Early goal-directed therapy (EGDT) consists of early, aggressive fluid resuscitation and is known to improve survival in sepsis. It is unknown how often EGDT leads to subsequent fluid overload and whether post-EGDT fluid overload affects patients’ outcomes. Our hypothesis was that patients with sepsis treated with EGDT were at risk for fluid overload and that fluid overload would be associated with adverse outcomes. We conducted a retrospective cohort of 405 consecutive patients admitted with severe sepsis and septic shock to the medical intensive care unit of a tertiary care academic hospital from January 2008 to December 2009. Baseline demographics, daily weights, fluid status, clinical or radiographic evidence of fluid overload, and medical interventions (thoracentesis, paracentesis, diuretic use, and ultrafiltration) were abstracted, and associations explored using univariate and multivariate logistic and linear regression analyses. At day 1, 67% of patients developed evidence of fluid overload, and in 48%, fluid overload persisted to day 3. Interrater agreement for presence of fluid overload was substantial (κ = 0.7). An increased trend in weight was noted in those with persistent clinical and radiologic evidence of fluid overload, but not with recorded positive fluid balance. When adjusted for baseline severity of illness, fluid overload was associated with increased use of fluid-related medical interventions (thoracentesis and diuretics) and hospital mortality (odds ratio, 1.92; confidence interval, 1.16–3.22). In patients with severe sepsis and septic shock treated with EGDT, clinical evidence of persistent fluid overload is common and is associated with increased use of medical interventions and hospital mortality.