Raised systemic levels of interleukin (IL)-6 and IL-10 cytokines have been associated with poorer outcome in community-acquired pneumonia. The aim of our study was to identify potential associated factors with increased levels of IL-6, IL-10, or both cytokines. We performed a prospective study of 685 patients admitted to hospital with community-acquired pneumonia. IL-6 and IL-10 were measured in blood in the first 24 h. 30-day mortality increased from 4.8% to 11.4% (p=0.003) when both cytokines were higher than the median. Independent associated factors with an excess of IL-6 were neurologic disease, confusion, serum sodium <130 mEq·L-1, pleural effusion, and bacteraemia. The associated factors for an excess of IL-10 were respiratory rate ≥30 breaths·min-1, systolic blood pressure <90 mmHg and glycaemia ≥250 mg·dL-1. The independent associated factors for an excess of both cytokines were confusion, systolic blood pressure <90 mmHg, pleural effusion and bacteraemia. Protective factors were prior antibiotic treatment and pneumococcal vaccination. Different independent factors are related to an excess of IL-6 and IL-10. Confusion, hypotension, pleural effusion and bacteraemia were associated with the inflammatory profile with the highest mortality rate, whereas anti-pneumococcal vaccination and previous antibiotic treatment appeared to be protective factors. Copyright©ERS 2011.