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Lower life expectancy in men is generally attributed to higher likelihood of risky behavior and because men develop chronic conditions earlier. If sex-related differences in survival are independent of preinfection chronic health and health behavior, it would suggest that survival differences may occur because of sex differences in quality of care and biological response to infection, and these differences may contribute to sex differences in life expectancy. We assessed if sex-related survival difference following community-acquired pneumonia (CAP) is due to differences in clinical characteristics, quality of care, or immune response.Prospective observational cohort of 2183 subjects with CAP.Mean age was 64.9 years. Men were more likely to smoke and had more comorbidity compared with women. At emergency department presentation, men had different biomarker patterns, as evidenced by higher inflammation (tumor necrosis factor, interleukin [IL]-6, and IL-10) and fibrinolysis (d-dimer), and lower coagulation biomarkers (antithrombin-III and factor IX) (p < 0.05). Small differences in favor of men were seen in care quality, including antibiotic timing and compliance with American Thoracic Society guidelines. Men had lower survival at 30, 90, and 365 days. The higher 1-year mortality was not attenuated when adjusted for differences in demographics, smoking, resuscitation, insurance, and vaccination status, comorbidity, hospital characteristics, and illness severity (unadjusted hazard ratio [HR] = 1.35, p = 0.003; and adjusted HR = 1.29, p = 0.004). HR was no longer statistically significant when additionally adjusted for differences in emergency department concentrations of tumor necrosis factor, IL-6, IL-10, d-dimer, antithrombin-III, and factor IX (adjusted HR = 1.27, p = 0.17). Patterns of biomarkers observed in men were associated with worse survival for 1 year.Lower survival among men following CAP was not explained by differences in chronic diseases, health behaviors, and quality of care. Patterns of inflammatory, coagulation, and fibrinolysis biomarkers among men may explain reduced short-term and long-term survival.