We sought to quantify patient morbidity throughout Pseudomonas aeruginosa bloodstream infection (PABSI) as a function of patient covariates. Individuals with PABSI were included in a retrospective, observational, cohort study. Morbidity was quantified by serial Sequential Organ Failure Assessment (SOFA) scores. Impact of active antimicrobial treatment was assessed as a function of changes in SOFA scores as the dependent variable. A total of 95 patients with PABSI were analyzed. Relative to baseline SOFA scores (day -2), scores after PABSI were increased by 37% on day 0 and 22% on day +2 but returned to baseline on day +7. Overall mortality was 37%, and mean length of hospital stay (postculture) was 16 days. Most patients were appropriately treated, with n = 83 (87%) receiving an active agent and n = 61 (64%) receiving >1 agent. As a result, an effect of therapy on morbidity was not observed. Advanced age and elevated baseline SOFA scores predicted increased in-hospital mortality (P = 0.01 and P < 0.001, respectively) and morbidity at day +2 (P < 0.05 and P < 0.05, respectively) and day +7 (P < 0.05 and P < 0.001, respectively). Neutropenia was also associated with increased morbidity at day +2 (P < 0.05). In treated PABSI, morbidity is highest the day of the diagnostic blood cultures and slowly returns to baseline over the subsequent 7 days. Age and baseline severity of illness are the strongest predictors of morbidity and mortality. Because neither of these factors are modifiable, efforts to minimize the negative impact of PABSI should focus on appropriate prevention and infection control efforts.