OBJECTIVES: To determine the effect of exercise interventions on mental health and health-related quality of life (HRQoL) in individuals with SCI. DATA SOURCES: We searched Embase, CINAHL, Medline, PsychINFO, and SPORTDiscus from inception to September 2023. STUDY SELECTION: We included randomized controlled trials that (1) involved participants >= 18 years old with a SCI; (2) administered an exercise intervention; and (3) measured subjective well-being, psychological well-being, social well-being, and/or HRQoL as outcomes. We reported standardized means differences (d) with a 95% confidence interval (CI), assessed the risk of bias by using the Revised Cochrane Risk-of-bias Tool for Randomized Trials (RoB 2), and the certainty of the evidence using GRADE. DATA SYNTHESIS: Nineteen studies (797 participants, mean age < 65 years in every study) were included. Exercise improved overall well-being (d 0.494; 95% CI 0.268 to 0.720; low certainty evidence), subjective well-being (d 0.543; 95% CI 0.270 to 0.816; low certainty evidence), psychological well-being (d 0.499; 95% CI 0.193 to 0.805; low certainty evidence), social well-being (d 0.452; 95% CI 0.151 to 0.752; low certainty evidence), and HRQoL (d 0.323; 95% CI 0.072 to 0.574; low certainty evidence). Four serious adverse events probably attributable to the interventions were reported in 3 studies. CONCLUSIONS: Exercise interventions can improve well-being and HRQoL in adults with SCI < 65 years of age. Additional research is needed to determine effectiveness in adults >= 65 years of age.

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