PURPOSE: Given the benefits of exercise for cancer survivors, scalable exercise intervention strategies are needed to help survivors be more active. This study used Multiphase Optimization Strategy (MOST) to test behavior change strategies of an evidence-based diet and exercise intervention for patients with chronic lymphocytic leukemia (CLL), examining the effects on physical activity (PA) participation, self-efficacy and social support for exercise, and quality of life (QOL). METHODS: The HEALH4CLL study provided a Fitbit and 16 weekly educational materials about exercise, diet, and weight management. Patients with CLL were randomly assigned to 1 of 16 combinations of behavioral change strategies: email vs. telephone coaching; text message reminder vs. none; resistance plus aerobic exercise vs. aerobic exercise alone; and daily vs. weekly self-monitoring. Patients’ Godin Leisure Time Activity Questionnaire, PROMIS physical and mental health, Exercise Self-efficacy, and Sallis’ Social Support for Exercise were assessed at baseline and follow-up. Effectiveness of intervention components on PA, QOL, exercise self-efficacy, and social support for exercise from family and friends among patients with CLL were examined using paired t-tests and factorial analysis of variance. RESULTS: 31 patients were completed the intervention (mean age 63 yrs; 57% female; 89% white). We observed significant increases in PA scores (+14.5, t = 4.46, p < .001), physical health t-scores (+2.3, t = 2.45, p = .020), and family social support sum of scores (+4.1, t = 3.33, p = .002) in all patients after the intervention. According to factorial analysis, combined resistance and aerobic exercise with daily self-monitoring was effective for improvement of PA scores (+16.0, t = 2.18, p = .042) and physical health related to QOL t-scores (+4.4, t = 2.34, p = .030). Social support for exercise from friends score was affected by daily self-monitoring (+4.2, t = 2.47, p = .024) and email coaching with text reminder (+4.3, t = 2.47, p = .024). CONCLUSIONS: This study demonstrated that combination of resistance and aerobic exercise, daily self-monitoring, email coaching, and text message reminders were effective for increases in PA, physical health related QOL, and social support from friends.