OBJECTIVES: Many older cancer survivors are overweight or obese, with additional illness burden increasing functional decline, which may affect their ability to engage in lifestyle interventions. This study examined how overweight long-term survivors' symptom severity associated with comorbidity prior to a diet and exercise intervention was associated with post-intervention function and examined symptoms' effects on function through change in physical activity, diet quality, and weight status. MATERIALS AND METHODS: This is a secondary data analysis of 514 breast, prostate, and colorectal cancer survivors who participated in the one-year home-based diet and exercise intervention Reach-Out to Enhance Wellness trial. Measures included symptoms, weight, physical activity, diet quality, overall physical function (PF), and basic and advanced lower extremity function (BLEF and ALEF). Simple and serial mediation analyses were conducted to examine direct effects of symptom severity on PF, BLEF, and ALEF and indirect effects of symptom severity through changes in diet quality, physical activity, and weight. RESULTS: Symptom severity was directly associated with lower functioning scores for PF (b=-0.63 p<0.001), BLEF (b=-0.33, p<0.001), and ALEF (b=-0.22, p<0.001). Indirect effects of symptom severity through weight loss, physical activity, and diet were not significant. Weight loss and physical activity were associated with higher PF and ALEF and diet quality was associated with higher BLEF. CONCLUSION: Symptom severity of older, overweight cancer survivors negatively affects physical function. However, greater weight loss and more physical activity were associated with higher functioning scores, regardless of symptom severity.