This study investigated how perceived stress, social support, and home-based physical activity affected older adults' fatigue, loneliness, and depression. We also explored whether social support and physical activity mediated the relationships between stress and mental health problems. The data of 163 older participants were analyzed in this study. Structural equation modeling using LISREL 8.71 was performed to assess the effects of stress, support, and physical activity on mental health. The findings indicate that perceived stress predicted higher levels of depression, social support predicted lower levels of loneliness and fatigue, and physical activity predicted lower levels of fatigue among older adults. Social support and physical activity mediated the relationships between stress and mental health, except depression. In conclusion, the relative impacts of perceived stress, social support, and physical activity on types of mental health (e.g., fatigue, loneliness, and depression) were different. Furthermore, stress had direct and indirect effects on each construct of mental health (e.g., fatigue, loneliness, and depression).