Low red blood cells, a condition called anemia, happens when your body either isn’t making enough red blood cells, is destroying them too fast, or is losing them through bleeding. Normal red blood cell counts range from 4.35 to 5.65 million per microliter of blood for men and 3.92 to 5.13 million for women. When counts drop below these ranges, or hemoglobin falls below 13.5 g/dL in men or 12.0 g/dL in women, your tissues receive less oxygen and you start feeling the effects: fatigue, weakness, shortness of breath, and pale skin.
The causes range from something as straightforward as not getting enough iron in your diet to serious conditions like bone marrow failure. Understanding the specific cause matters because treatment depends entirely on what’s driving the problem.
Iron Deficiency
Iron deficiency is the single most common cause of low red blood cells worldwide. Your bone marrow needs iron to build hemoglobin, the protein inside red blood cells that carries oxygen. Without enough iron, the marrow can’t assemble functional hemoglobin, and the red blood cells it produces are smaller and paler than normal.
This doesn’t happen overnight. Iron deficiency develops in stages. First, your bone marrow’s iron stores gradually deplete while your gut compensates by absorbing more iron from food. In the next stage, the iron supply to developing red blood cells drops low enough that production slows down. In the final stage, your red blood cells shrink in size and your hemoglobin drops, producing the classic symptoms of anemia. Heavy menstrual periods, pregnancy, a diet low in red meat or leafy greens, and conditions that reduce iron absorption (like celiac disease) are the most frequent triggers.
Vitamin B12 and Folate Deficiency
While iron deficiency makes red blood cells too small, a lack of vitamin B12 or folate does the opposite. These vitamins are essential for building DNA. Without them, developing red blood cells can’t divide properly. The cells keep growing larger while their internal machinery falls behind, producing oversized, immature cells called megaloblasts that don’t function well and often die before leaving the bone marrow.
B12 deficiency is common in people who eat little or no animal products, since meat, eggs, and dairy are the primary dietary sources. It also occurs in people with conditions that impair absorption in the gut, such as pernicious anemia (an autoimmune condition affecting the stomach lining) or Crohn’s disease. Folate deficiency tends to stem from poor dietary intake of leafy greens and legumes, heavy alcohol use, or certain medications that interfere with folate metabolism.
Chronic Kidney Disease
Your kidneys do more than filter waste. They also produce a hormone called erythropoietin (EPO) that signals the bone marrow to make red blood cells. Specialized cells in the kidneys sense when oxygen levels in the blood are low and ramp up EPO production in response. As kidney function declines, these cells lose the ability to produce adequate EPO, and red blood cell production drops with it.
Anemia becomes more prevalent and severe the further kidney function falls. This is one reason people with advanced kidney disease often feel persistently exhausted, even when other aspects of their condition are managed. The anemia tends to develop gradually, sometimes going unnoticed until a routine blood test reveals it.
Chronic Inflammation and Infection
Long-term inflammatory conditions like rheumatoid arthritis, lupus, inflammatory bowel disease, and chronic infections can lower red blood cell counts through a surprising mechanism: your body intentionally withholds iron from the bloodstream.
During inflammation, the immune system produces signaling molecules (especially one called IL-6) that trigger the liver to release a protein called hepcidin. Hepcidin acts like a gatekeeper. It blocks iron from being absorbed in the gut and traps iron inside immune cells, preventing it from being recycled back into the bloodstream. The result is that even if you have adequate iron stored in your body, very little of it reaches the bone marrow to make new red blood cells. This is why anemia caused by chronic disease can look like iron deficiency on some blood tests but doesn’t respond to iron supplements alone.
Blood Loss
Losing blood means losing red blood cells directly, and when the loss is slow and steady, it can drain your supply without obvious symptoms. The most common source is the gastrointestinal tract. Peptic ulcers, hemorrhoids, colon polyps, diverticulosis, inflammatory bowel disease (ulcerative colitis and Crohn’s disease), and cancers of the colon, stomach, or esophagus can all cause bleeding that ranges from barely detectable to severe. Tears or inflammation in the esophagus are another source.
What makes chronic GI bleeding particularly tricky is that you may not see blood in your stool, especially if the bleeding originates high in the digestive tract. Over weeks or months, this hidden blood loss depletes your iron stores and gradually lowers your red blood cell count. Heavy menstrual bleeding is another major cause, particularly in women of reproductive age, and is often underrecognized as a source of significant iron loss.
Red Blood Cell Destruction
Sometimes the body makes enough red blood cells, but they’re being destroyed faster than they can be replaced. This group of conditions is called hemolytic anemia, and the causes fall into two broad categories.
External causes include autoimmune conditions where the immune system mistakenly attacks its own red blood cells, certain medications (including some antibiotics and antimalarials), mechanical damage from defective heart valves or other implants, severe infections, snake venom, and a group of blood vessel disorders where tiny clots shred red blood cells as they pass through narrowed vessels.
Internal causes are usually inherited. In conditions like sickle cell disease, red blood cells are built with abnormal hemoglobin that causes them to deform and break down prematurely. In thalassemia, the body produces too little of one of hemoglobin’s protein chains, leading to fragile red blood cells that don’t survive their normal 120-day lifespan. The spleen, which filters the blood, removes these damaged or abnormal cells from circulation. When the spleen is enlarged, it can become overactive and clear even mildly abnormal cells, worsening the anemia.
Bone Marrow Failure
Red blood cells are manufactured inside the bone marrow, so anything that damages or displaces the marrow directly impacts production. In aplastic anemia, the marrow stops producing enough blood cells of all types, not just red blood cells. This condition can develop after exposure to certain chemicals (especially benzene and pesticides), some medications including sulfonamides and antiseizure drugs, viral infections like hepatitis, or autoimmune attack on the marrow itself. In many cases, no clear trigger is identified.
Myelodysplastic syndromes are a related group of conditions where the bone marrow produces blood cells that are abnormal and don’t mature properly. Risk factors include long-term exposure to benzene, tobacco, and pesticides, as well as prior radiation or chemotherapy for cancer. Inherited bone marrow failure syndromes, such as Fanconi anemia and Diamond-Blackfan anemia, are rarer causes that typically appear in childhood.
Cancers that originate in or spread to the bone marrow, including leukemia, lymphoma, and multiple myeloma, can crowd out healthy blood-producing cells and significantly reduce red blood cell output.
Other Common Contributors
Several other factors can lower red blood cell counts without fitting neatly into the categories above. Hypothyroidism slows metabolism throughout the body, including in the bone marrow. Liver disease can contribute to anemia through multiple mechanisms, including bleeding, poor nutrition, and changes in how the body processes iron. Certain medications, particularly chemotherapy drugs and some HIV treatments, suppress the bone marrow as a side effect.
Pregnancy increases blood volume faster than the body can produce new red blood cells, often causing a dilutional anemia even in otherwise healthy women. This is one reason iron and folate supplementation is standard during pregnancy. Endurance athletes occasionally develop mild anemia from a combination of increased red blood cell destruction during intense exercise and expanded blood volume.
Because the causes of low red blood cells are so varied, a single blood test showing anemia is just the starting point. Additional tests, including iron levels, vitamin levels, kidney function, and sometimes a close look at the blood cells themselves under a microscope, help pinpoint the specific cause and guide the right treatment.