Physical and social distancing guidelines have been introduced across many US states to minimize community transmission of COVID-19. We hypothesized that social distancing behaviors may pose a barrier to the participation in habitual physical activity for the general population. PURPOSE: To determine whether engaging in social distancing behaviors predicts physical activity level of the US public. METHODS: We developed an online questionnaire: the COVID-19 Physical Activity and Wellbeing Survey (PAWS). Social media was used to recruit 4,819 respondents (Median age: 46 years [IQR: 35-59]; 51.3% female) from the US population during April through June 2020. The survey included questions on adherence to 11 social distancing behaviors, and validated questionnaires which assessed self-reported physical activity and sedentary behavior (Global Physical Activity Questionnaire; GPAQ), depression (Patient Health Questionnaire; PHQ-9), anxiety (Generalized Anxiety Disorder 7-item scale; GAD-7) and mental wellbeing (World Health Organization 5-item wellbeing scale; WHO-5). Physical activity level was categorized into 4 distinct groups: inactive (0 MET-min·week-1); low (1-599 MET-min·week-1); moderate (600-2999 MET-min·week-1); and high (≥3000 MET-min·week-1). An ordinal generalized additive model (GAM) was used to determine which social distancing factors predicted physical activity level, after accounting for demographic, socioeconomic, and mental health variables. RESULTS: The GAM analysis revealed that wearing a facemask in public (OR: 1.60 [1.34-1.92]), limiting use of public transport (OR: 1.29 [1.08-1.54]), and restricting travel outside the house (OR: 1.21 [1.02-1.43]) were social distancing behaviors associated with higher odds of being more physically active (P < 0.05). Conversely, working from home (OR: 0.84 [0.74-0.95]) and avoiding physical activity outside the house (OR: 0.76 [0.66-0.88]) were associated with higher odds of being less physically active (P < 0.05). CONCLUSIONS: Our findings highlight that working from home and avoiding outdoor physical activity may negatively impact on physical activity levels of the general public during the COVID-19 pandemic.