Background: Cancer patients often describe poor sleep quality and sleep disruption as contributors to poor quality of life (QoL). In a cross-sectional study of post-treatment breast, endometrial, and melanoma cancer patients, we used actigraphy to quantify sleep regularity using the sleep regularity index (SRI), and examined relationships with reported sleep symptoms and QoL.Methods: Participants were recruited post-primary treatment (35 diagnosed with breast cancer, 24 endometrial cancer, and 29 melanoma) and wore an actigraphy device for up to 2 weeks and SRI was calculated. Self-report questionnaires for cancer-related QoL [European Organization for Research and Treatment of Cancer EORTC (QLQ-C30)] were completed. Data were compared using analysis of variance (ANOVA) or Chi-Square tests. Multivariate linear regression analysis was used to determine independent variable predictors for questionnaire-derived data.Results: Age distribution was similar between cohorts. Endometrial and breast cancer cohorts were predominantly female, as expected, and body mass index (BMI) was higher in the endometrial cancer cohort, followed by breast and melanoma. There were no differences between tumor groups in: total sleep time, sleep onset latency, bedtime, and SRI (breast 80.9 ± 8.0, endometrial 80.3 ± 12.2, and melanoma 81.4 ± 7.0) (all p > 0.05). A higher SRI was associated with both better functional and symptom scores, including increased global QoL, better physical functioning, less sleepiness and fatigue, better sleep quality, and associated with less nausea/vomiting, dyspnea, and diarrhea (all p < 0.05).Conclusion: In cancer patients post-treatment, greater sleep regularity is associated with increased global QoL, as well as better physical functioning and fewer cancer related symptoms. Improving sleep regularity may improve QoL for cancer patients.