Pneumonia is the most common cause of sepsis. Lung infections account for roughly half of all severe sepsis cases, far outpacing any other infection site. Each year, at least 1.7 million adults and more than 18,000 children in the U.S. develop sepsis, and at least 350,000 adults die during their hospitalization or are discharged to hospice care.
Infections That Lead to Sepsis
Sepsis isn’t a disease on its own. It’s what happens when your body’s response to an existing infection spirals out of control and starts damaging your own organs. Almost any infection can trigger it, but some types are far more likely to do so than others.
CDC data breaks down the infections most frequently identified before a sepsis admission: pneumonia leads at 35%, followed by urinary tract infections at 25%, gastrointestinal infections at 11%, and skin or soft tissue infections at 11%. In studies focused specifically on severe sepsis, pulmonary infections account for an even larger share, around 50%, with abdominal infections at 24% and urinary tract sources at 5 to 7%. The pattern is slightly different in children, where respiratory infections still lead (29%) but gastrointestinal infections follow closely at 24%.
Bacteria Behind Most Cases
When sepsis develops from a bacterial infection, two organisms dominate. E. coli, a bacterium commonly found in the gut, is the single most frequent cause of bloodstream infections, responsible for about 27% of cases. It’s the usual culprit when a urinary tract or abdominal infection progresses to sepsis. Staphylococcus aureus, which lives on skin and in the nasal passages, runs at a nearly identical incidence rate of roughly 65 cases per 100,000 people per year. Staph is more often linked to skin infections, surgical wounds, and infections related to catheters or other medical devices.
Other bacteria play significant roles too, including Streptococcus species (a common cause of pneumonia) and various hospital-acquired organisms that may be resistant to standard antibiotics. But E. coli and S. aureus together account for the largest share of bacterial sepsis by a wide margin.
Viruses Can Cause Sepsis Too
Sepsis isn’t limited to bacterial infections. The COVID-19 pandemic made that dramatically clear. From March 2020 through November 2022, the virus responsible for COVID-19 accounted for roughly one in six sepsis cases in hospitalized patients. Among people hospitalized with COVID, 28.2% developed sepsis. Early in the pandemic, the mortality rate for virus-associated sepsis was 33%, though it eventually declined to about 14.5%, roughly matching the death rate for bacterial sepsis.
Influenza and other respiratory viruses can also trigger sepsis, particularly in older adults and people with weakened immune systems. The mechanism is the same regardless of whether a virus or bacterium starts the process.
How Infection Becomes Sepsis
Your immune system fights infections by releasing signaling molecules called cytokines, which recruit immune cells to the infection site. In sepsis, this process goes haywire. Elevated levels of immune cells secrete even more cytokines, which recruit still more immune cells, creating a self-reinforcing cycle sometimes called a “cytokine storm.” Instead of containing the original infection, the immune response begins attacking your own tissues and organs. Blood pressure can drop dangerously, oxygen delivery to organs falters, and without treatment, organ failure and death follow.
This is why sepsis can progress so quickly. The damage comes not just from the infection itself but from your body’s own defense system turning against you.
Who Faces the Highest Risk
Most people who develop sepsis have at least one underlying medical condition or a recent hospitalization. The groups at greatest risk include adults 65 and older, children younger than one, and anyone with a chronic condition like diabetes or lung disease. About one in five sepsis hospitalizations are cancer-related, and people with end-stage kidney disease on dialysis face elevated risk as well. Pregnant and postpartum women are also more vulnerable because pregnancy alters immune function and often involves medical procedures that can introduce infection.
Between 10 and 15% of adult sepsis cases actually begin in the hospital, often tied to surgical sites, catheters, or ventilators. Overall, 72% of patients who developed sepsis either had contact with the healthcare system in the month before admission or had a chronic condition requiring frequent medical care. That statistic suggests many cases could potentially be caught earlier if both patients and providers recognized the warning signs of a worsening infection: fever or abnormally low temperature, rapid heart rate, confusion, and extreme fatigue or pain that seems disproportionate to the infection.
People who survive sepsis also face a higher risk of developing it again in the future. Most survivors recover fully, but the experience resets your baseline risk upward, making it important to take even routine infections seriously going forward.