Rationale Current murine models of sepsis do not account for the effects of aggressive fluid resuscitation on hemodynamics and mortality. Objectives Evaluate the impact of fluid resuscitation regimens on cardiovascular performance and survival in a murine model of sepsis. Methods Mice ( n  = 90) were made septic by cecal ligation and puncture (CLP), and received antibiotics plus Low, Intermediate , or High fluid resuscitation regimens. Stroke volume (SV), cardiac output (CO), and fractional shortening (FS) were measured by echocardiography at predefined time points. Measurements and main results Baseline echocardiographic measurements were similar in all groups. After CLP, SV and CO decreased early in all groups; High: 57.2 ± 9.2 to 23.9 ± 7.2 µL, and 26.8 ± 4.9 to 13.1 ± 5.8 ml/min; Intermediate: 52.1 ± 7.0 to 21.5 ± 6.6 µL, and 24.9 ± 4.1 to 11.9 ± 3.9 ml/min; Low: 54.0 ± 7.0 to 20.3 ± 5.6 µL, and 25.8 ± 4.0 to 11.3 ± 3.9 ml/min ( P  < 0.05 for all vs. baseline). With resuscitation there was a dose-dependent improvement in SV and CO ( P  < 0.05). At 24 h SV and CO were 44.0 ± 13.8 µL and 20.7 ± 8.5 ml/min in the High group, 39.8 ± 12.3 µL and 16.7 ± 6.5 ml/min in the Intermediate group, and 30.1 ± 12.4 µL and 14.0 ± 7.2 ml/min in the Low group. Survival was improved in the High fluid group (75%) compared to the Intermediate (58%) and the Low (35%) resuscitation groups ( P  < 0.05). Conclusions In this model, as in human sepsis, the intensity of fluid resuscitation modulates hemodynamic response and mortality. Incorporation of early and aggressive fluid resuscitation can significantly enhances the clinical relevance of murine models of sepsis.