This study employed a pre-post design to examine the relationship between physical activity (PA) and mental health among college students (N = 743) at the end of the semester. Data on PA and mental health indicators, including stress, anxiety, and depression, were collected during the third week of the semester and the week before final exams. Results revealed a significant decline in PA levels from an average of 2381.18 MET-min/week at the beginning of the semester to 1818.53 MET-min/week at the end. Concurrently, stress, anxiety, and depression levels increased significantly. Regression analyses indicated that PA at the end of the semester significantly predicted lower levels of stress (beta = -0.115, p < 0.001) and depression (beta = -0.058, p = 0.047) after controlling for baseline measures, but was not significantly associated with anxiety, even after controlling for age, gender, and initial levels of these indicators at the beginning of the semester.