Hydroxychloroquine does not meaningfully increase your risk of getting sick. Unlike stronger immune-suppressing drugs used for autoimmune conditions, hydroxychloroquine modulates the immune system rather than broadly suppressing it. The American College of Rheumatology states directly that this drug “is not known to suppress your immune system.” That said, the reality is slightly more nuanced than a simple no, especially when it comes to vaccine responses.
How Hydroxychloroquine Affects Your Immune System
Your immune cells rely on tiny acidic compartments called lysosomes to break down invaders and activate inflammatory signals. Hydroxychloroquine accumulates inside these compartments and raises their pH, making them less acidic. This disrupts the sensors (called toll-like receptors) that normally detect threats and trigger inflammation. The result is a dampening of certain inflammatory pathways rather than a wholesale shutdown of immune defense.
This is why hydroxychloroquine works well for conditions like lupus and rheumatoid arthritis. It dials down the overactive immune signaling that causes joint pain, rashes, and organ damage without leaving you as vulnerable to infections as more aggressive medications do. In laboratory settings, researchers have confirmed that hydroxychloroquine has a “profound effect” on these inflammatory pathways in isolated cells, but the systemic effect in the whole body is considerably more limited.
What the Infection Data Actually Shows
Multiple large studies have looked at whether people taking hydroxychloroquine get more infections, and the consistent finding is that they don’t. A population-based study of over 3,200 patients with rheumatic diseases found no significant difference in bacterial pneumonia rates between hydroxychloroquine users and non-users. Patients who took the drug for more than about four years actually had a 45% lower risk of bacterial pneumonia compared to those not taking it.
Data from a lupus registry found that hydroxychloroquine tended to reduce the risk of severe infections, with an odds ratio of 0.59, meaning users were roughly 40% less likely to develop a serious infection. That result didn’t quite reach statistical significance, but it pointed in a protective direction. The drugs that did significantly increase infection risk in that study were corticosteroids and other immunosuppressants.
Opportunistic infections, the kind caused by organisms that typically only affect people with weakened immune systems (certain fungi, tuberculosis-related bacteria), show no increased incidence with hydroxychloroquine use. This is a key distinction from drugs like methotrexate, which can cause bone marrow suppression and carries a meaningfully higher rate of serious adverse events. In one study comparing the two drugs in older adults with kidney disease, the 90-day risk of serious adverse events was roughly twice as high with methotrexate (3.55%) as with hydroxychloroquine (1.73%).
The Vaccine Response Question
One area where hydroxychloroquine does appear to have a real effect is vaccine responses. Because the drug interferes with the same cellular machinery your immune system uses to process vaccine components and build antibodies, some vaccines may work less effectively while you’re taking it.
A study of yellow fever vaccination in patients with Sjögren’s syndrome found that only 69% of those on hydroxychloroquine developed protective antibody levels, compared to 96% of healthy controls and 94% of patients with the same condition who weren’t taking the drug. Research has also shown reduced antibody responses to the pneumococcal conjugate vaccine in patients with lupus-related skin disease taking hydroxychloroquine, and similar effects have been documented with oral cholera and rabies vaccines.
This doesn’t mean vaccines are pointless if you take hydroxychloroquine. Most people still mount a response. But it’s worth knowing that your protection from certain vaccines may be somewhat lower than average, which is something to factor into decisions about boosters or travel vaccinations.
Flu-Like Symptoms vs. Actual Infections
One thing that may fuel concern about illness susceptibility is that hydroxychloroquine itself can cause flu-like symptoms as a side effect. In one clinical trial, 29% of participants in the hydroxychloroquine group reported influenza-like illness compared to 10% in the placebo group. These symptoms (headache, fatigue, general malaise) can feel like getting sick even when no infection is present. If you’ve started hydroxychloroquine and feel like you’re catching more colds, the drug’s own side effect profile may be the explanation rather than an actual increase in infections.
Long-Term Use and Cumulative Effects
People with lupus or rheumatoid arthritis often take hydroxychloroquine for years or even decades, which naturally raises the question of whether the drug gradually weakens immune defenses over time. The available evidence suggests the opposite. The pneumonia study mentioned earlier found that longer use (beyond four years) was associated with lower, not higher, infection risk. This likely reflects hydroxychloroquine’s ability to keep the underlying autoimmune disease under better control, since uncontrolled autoimmune inflammation is itself a major risk factor for infections.
The drug does accumulate in tissues with extended use, which is why eye exams are recommended to monitor for retinal toxicity. But this tissue accumulation doesn’t translate into progressive immune suppression. The immune-modulating effects appear to reach a steady state rather than deepening over time.
How It Compares to Other Autoimmune Drugs
If you’re taking hydroxychloroquine and wondering about your infection risk, context matters. Among the drugs commonly used for autoimmune diseases, hydroxychloroquine sits at the mildest end of the spectrum:
- Hydroxychloroquine: No significant increase in infection rates, no opportunistic infections, not classified as immunosuppressive
- Methotrexate: Roughly double the rate of serious adverse events compared to hydroxychloroquine, including serious infections and bone marrow suppression
- Corticosteroids: Significantly associated with severe infections in lupus patients, with risk nearly doubling for each step up in dose
- Biologic immunosuppressants: Carry boxed warnings about serious infections including tuberculosis and invasive fungal diseases
Hydroxychloroquine’s safety profile is one reason rheumatologists consider it a foundational treatment for lupus and often continue it even when adding stronger medications. It manages disease activity with minimal trade-off in immune defense, which is a rare combination in autoimmune treatment.