Objective: The objective of the study was to determine the association between positive cumulative fluid balance following heat stroke (HS) and its impact on patient outcomes.Methods: A retrospective chart review of HS patients admitted to the emergent intensive care unit (ICU), Beijing Lu He Hospital, Capital Medical University, from 2015 to 2018 was conducted.Results: Forty-nine surviving HS patients met the inclusion criteria. Patients were divided into two groups based on the median duration of mechanical ventilation (MV). Patients with MV for more than 6 days were placed in the longer length of the MV group. Patients with MV for <6 days were placed in the shorter MV group. There were significant differences between the two groups regarding the fluid balance on day 2 (3040 ml vs. −533 ml, P = 0.017) and persistent cumulative fluid overload in the first 72 h (6112 ml vs. −46 ml, P = 0.04). Patients with a higher cumulative fluid overload in the first 72 h were more likely to receive a longer duration of MV (10.7 days vs. 3.2 days, P < 0.001) and ICU length of stay (22.5 days vs. 6.2 days, P < 0.001). Spearman analysis of fluid overload in the first 72 h and MV time showed that the correlation coefficient was 0.662. Binary logistic regression analysis showed that the positive cumulative fluid balance in the first 72 h (odds ratio [OR] = 1, 95% confidence interval [95% CI] = 0.99–1.01] and alanine aminotransferase (OR = 0.978, 95% CI = 0.95–0.99) were both independent risk factors for prolonged MV in patients with HS (P = 0.025, P = 0.026). There were also differences between groups regarding creatine kinase-MB (P = 0.01) and Glasgow Coma Scale scores (P = 0.033). The patients with a higher cumulative fluid overload in the first 72 h had larger sequential organ failure assessment cores. Based on the receiver operating characteristic analysis, the cumulative fluid overload in the first 72 h predicted the need for invasive MV with the area under the curve of 0.869 (P < 0.0001, 95% CI: 0.779–0.958) at a cutoff value >1685 ml (sensitivity: 86%; specificity: 78%).Conclusions: Fluid overload in the first 72 h was a predictor of prolonged MV and ICU length of stay in surviving HS patients. Maintaining cautious about fluid resuscitation for HS patients may be critical for improving patient outcomes.