IV fluids are recommended to adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists. Do lower vs higher fluid volumes improve patient-important outcomes in adult patients with sepsis? We updated a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials assessing lower vs higher IV fluid volumes in adult patients with sepsis. The coprimary outcomes were all-cause mortality, serious adverse events (SAEs), and health-related quality of life (HRQoL). We followed the recommendations by the Cochrane Handbook and used the Grading of Recommendations Assessment, Development and Evaluation approach. Primary conclusions were based on low risk of bias trials if available. We included 13 trials (N = 4,006) with four trials (n = 3,385) added to this update. The meta-analysis of all-cause mortality in eight low risk of bias trials showed a relative risk of 0.99 (97% CI, 0.89-1.10; moderate certainty evidence). Six trials with predefined definitions of SAEs showed a relative risk of 0.95 (97% CI, 0.83-1.07; low certainty evidence). HRQoL was not reported. Among adult patients with sepsis, lower IV fluid volumes probably result in little to no difference in all-cause mortality compared with higher IV fluid volumes, but the interpretation is limited by imprecision in the estimate, which does not exclude potential benefit or harm. Similarly, the evidence suggests lower IV fluid volumes result in little to no difference in serious adverse events. No trials reported on HRQoL. PROSPERO; No.: CRD42022312572; URL: https://www.crd.york.ac.uk/prospero/.