Background: Early aggressive fluid resuscitation is beneficial in the management of septic shock (SS). Recent studies show that more positive or higher fluid balances after initial resuscitation in septic shock are associated with adverse outcomes. This study aimed to determine the impact of fluid balance on intensive care unit (ICU) mortality, and length of stay (LOS). Methods: A 4-year longitudinal retrospective study was conducted at the ICU of the Douala General Hospital (DGH). We reviewed file records of patients ≥ 18 years old, and with an ICU LOS of > 12 hours, admitted with a diagnosis of SS. We recorded the sociodemographic data, comorbidities, severity of illness as measured by the Sequential Organ Failure Assessment (SOFA), and modified Acute Physiologic and Chronic Health Evaluation (mAPACHE) II scores, treatment details, and patient’s outcome. We followed the fluid intake and balance during the first 3 days. Data were analyzed using a the software SPSS version 26. Survival analysis was done for different fluid balance quartiles. Multivariate logistic regression was used to control for confounders. Statistical significance was set at a p-value < 0.05. Results: 99 patients with an ICU mortality rate of 60.6% were recruited. Survivors had a significantly higher mean cumulative fluid intake within 48h (4.76 vs 3.64 L, p = 0.007) and 72 h (6.45 vs 4.53 L, p = 0.002). Non-survivors had a significantly higher mean fluid balance within 24 h (1.81 vs 0.64 L, p < 0.001) and cumulative fluid balance within 72 h (3.00 vs 1.45 L, p = 0.005). In multivariate logistic regression, mean cumulative fluid intake and fluid balance within 72 h were independently associated with ICU mortality (p = 0.016 (OR: 0.999) and 0.005 (OR; 1.001) respectively). There was no significant association between fluid balance and ICU LOS. Conclusions: Aggressive fluid resuscitation in septic shock is beneficial; however, a more positive fluid balance cumulatively over 3 days is associated ..