Objectives: The physical activity level (PAL) has significantly decreased as a result of the social distancing and lockdown related to the COVID‑19 pandemic, but there is a lack of knowledge on the correlates of PAL during the pandemic. The aim of this research was to examine the influence of pre-pandemic sports participation and substance use and misuse (SUM) on PAL during the COVID‑19 pandemic. Material and Methods: The study included 661 high-school students from Bosnia and Herzegovina (aged 15–18 years, 292 females). The investigation included 2 testing waves: before the COVID‑19 pandemic (baseline, January 2020) and during the COVID‑19 lockdown (follow-up, April 2020). The variables included PAL as measured by the Physical Activity Questionnaire for Adolescents, sports factors, and SUM. Results: Sports factors at baseline were positively correlated with PALs at both baseline and follow-up. Smoking tobacco negatively affected PALs at both baseline and follow-up. Alcohol consumption was positively correlated with PAL at baseline but had no effect on PAL at follow-up. Conclusions: This study confirmed the importance of sports participation in maintaining PAL during challenging situations, such as the COVID‑19 lockdown. The substance-specific influence of SUM on PAL before and during the lockdown points to evident social and cultural aspects of SUM behaviors in adolescents. Further studies evidencing the cumulative effects of PAL decline during the lockdown are warranted. Int J Occup Med Environ Health. 2021;34(2):151–63