Background & Aims Numerous randomized-controlled trials have shown that physical activity (PA) positively impacts cognitive and mental health outcomes throughout the lifespan, enhancing emotion-regulation skills. This suggests potential crossover effects on suicide-related outcomes closely tied to emotion regulation. Although cross-sectional studies, primarily in adults, exist on association of PA with suicidal ideation, no longitudinal study has yet explored PA's protective effect against non-suicidal self-injury (NSSI) in youth where NSSI is common. Utilizing population-based, prospectively collected data, our study aims to investigate both cross-sectional and longitudinal associations between PA and NSSI at the population level, laying the groundwork for future causal investigations. Methods This study included participants from the Québec Longitudinal Study of Child Development, a population-based cohort including 2120 individuals born in 1997/98 and follow until then. PA measures at 23 years of age were adapted from standardized and validated questionnaires (e.g. Enquête québécoise sur la santé de la population (EQSP) 2014-2015), exploring either frequency (number of days), intensity as well as energy expenditure of PA in commute as well as leisure PA. The frequency of NSSI was self-reported at 23 and 25 years of age. Preliminary correlations (Spearman) were investigated. Results Among around 1336 respondents, we found that at 23 years of age 10.2% reported last year NSSI, while at 25 years of age 7.0%. Interestingly, we found a significant negative correlation between the frequency (days per week) of leisure PA and NSSI at 23 (r Spearman = -0.069; P<0.012) and at 25 years of age (r = -0.053; P<0.060), whereas a positive correlation between the frequency (days per week) of commute PA and NSSI was found at 23 (r = 0.065; P<0.018) and 25 years of age (r =0.069; P<0.014). Moreover, a significant negative correlation between the leisure PA energy expenditure and NSSI at both 23 (r = 0.075; P<0.007) and 25 years of age (r = -0.047; P<0.099). Conclusions Preliminary data suggest that leisure PA may be a protective factor in young adults against NSSI. Further investigation will clarify cross-sectional and longitudinal associations, adjusting for confounding factors, using regression analyses.