The objective was to examine the relationship of duration and magnitude of arterial hypotension to subsequent cellular immune suppression and cytokinemia in patients hospitalized with community-acquired pneumonia (CAP). We studied an observational cohort of 525 subjects hospitalized after presenting to the emergency department with radiographic and clinical signs of CAP. We compared the duration and magnitude of hypotension, using the cardiovascular Sequential Organ Failure Assessment (CV SOFA) subscore, to day 3 monocyte expression of human leukocyte antigen-DR (mHLA-DR), a previously validated marker of cellular immune suppression. A significant association of CV SOFA with decreased mHLA-DR expression was present in univariate analysis (P < 0.001) and persisted after adjustment for illness severity and other covariates (P = 0.01). With CV SOFA separated into components of magnitude and duration, after covariate adjustment, only duration was associated with day 3 mHLA-DR expression (P = 0.03). Levels of key proinflammatory and anti-inflammatory cytokines (interleukin 6 [IL-6], IL-10, tumor necrosis factor) increased with hypotension exposure and were also associated with mHLA-DR expression. In patients admitted with CAP, arterial hypotension over the first 3 days is associated with markers of monocyte deactivation. The duration of exposure to hypotension may be more important than the magnitude, and monocyte deactivation correlates with IL-6 and IL-10 release. These results suggest that persistent hypotension might contribute to immunosuppression following septic shock.