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Objective: Mounting evidence suggests that antipsychotics may have immunomodulatory effects, but their impact on disseminated infections remains unknown. This study thus sought to estimate the effect of antipsychotic treatment on the occurrence of bloodstream infection during long-term follow-up in adult patients with chronic obstructive pulmonary disease., Methods: This retrospective cohort study, with new user and active comparator design, included adult patients seen from January 2008 to June 2018 in a tertiary teaching hospital in Buenos Aires, Argentina. New users of antipsychotic drugs were compared to new users of any benzodiazepine. The primary outcome of interest was incident bloodstream infection at 1 year of follow-up. Propensity score methods and a Cox proportional hazards model were used to adjust for baseline confounding., Results: A total of 923 patients were included in the present analysis. Mean (SD) age was 75.0 (9.8) years, and 51.9% of patients were female. The cumulative incidence of bloodstream infections at 1 year was 6.0% and 2.3% in the antipsychotic and benzodiazepine groups, respectively. Antipsychotic use was associated with a higher risk of bloodstream infections during the first year of follow-up (hazard ratio [HR] = 2.41; 95% CI, 1.13 to 5.14) compared to benzodiazepine use. Antipsychotics with high dopamine receptor affinity presented greater risk than less selective agents (HR = 5.20; 95% CI, 1.53 to 17.67)., Conclusions: Antipsychotic use is associated with bloodstream infections during the first year of follow-up in adult patients with chronic obstructive pulmonary disease. Further studies are warranted to confirm our findings and evaluate this effect in a broader population of patients., (© Copyright 2021 Physicians Postgraduate Press, Inc.)