Introduction. The COVID-19 pandemic has negatively impacted physical and mental health worldwide. It is essential to continue exploring the population’s psychological manifestations and the pandemic’s impact on lifestyles (physical activity, quality of sleep). Objective. This research aimed to describe the relationship between affect (positive and negative) and physical activity (PA) in college students during the COVID-19 pandemic. Method. A cross-sectional survey was conducted on health sciences students from three universities in Mexico and Colombia. PA was assessed using the short version of the International Physical Activity Questionnaire (IPAQ-S), and affects were measured using the PANAS index. A logistic regression model was used to assess the association between PA and affect. Results. We included 430 participants between 16 and 40 years. We found no differences between the male and female participants regarding age, weight (BMI), PA, or the number of hours of sitting per day. The monthly consumption of alcohol and tobacco was more frequent in males (p () .05), and women expressed having worse sleep quality (p () .05). Adjusting for the number of hours spent sitting per day, gender, BMI, age, sleep quality, smoking and alcohol consumption habits, participants reported having more positive affect when they engaged in greater PA. No association was found between PA and negative affect. Discussion and conclusion. Prioritizing mental health and assessments that determine the late impact of the COVID-19 pandemic on psychological well-being is critical. Promoting PA in university communities is considered a priority to positively impact students’ mental health and provide tools to facilitate coping.