STUDY OBJECTIVES: The aim of this study is to examine differences in sleep disruption and fatigue of men and women colorectal cancer (CRC) survivors with intestinal ostomies and associated health-related quality of life (HR-QOL). METHODS: Participants in this cross-sectional study of long-term (> 5 years) CRC survivors received care at Kaiser Permanente. Measures included the City of Hope QOL Ostomy questionnaire with narrative comments for ostomy-related ‘greatest challenges.’ The Short Form-36 Version 2 (SF-36v2) health survey provided physical (PCS) and mental composite scale (MCS) scores to examine generic HR-QOL. The ‘sleep disruption’ and ‘fatigue’ items from the ostomy questionnaire (scale from 0 to 10 with higher scores indicating better HR-QOL) were dependent variables, while independent variables included age, ethnicity, education, partnered status, body mass index, and time since surgery. Data were analyzed using chi-square for nominal variables, Student t-tests for continuous variables, and logistic regression with significance set at p < 0.05. RESULTS: On the ostomy-specific measure, women (n = 118) compared to men (n = 168) reported more sleep disruption (p < 0.01), adjusted for age, and greater levels of fatigue (p < 0.01), adjusted for time since surgery. Women's PCS and MCS scores indicated poorer HR-QOL compared to men, and differences were clinically meaningful. Qualitative narrative comments suggested that sleep disruption could stem from ostomy-associated fear of or actual leakage during sleep. CONCLUSION: Although women CRC survivors with ostomies report more sleep disruption and fatigue, which is reflected in their reduced physical and mental health scores on the SF-36v2 compared to men with ostomies, their stated reasons for disrupted sleep are similar to their male counterparts. These findings can provide a foundation for gender-relevant ostomy interventions to improve sleep and HR-QOL in this patient population.