Background Sexual dysfunction represents a critical aspect of quality of life for adolescent and young adult cancer survivors. Studies have consistently documented that adolescents and young adults report greater psychological and physical morbidity than older survivors and healthy peers, including elevated rates of sexual dysfunction, often accompanied by lower satisfaction with sex life and delays in meeting sexual milestones. Moreover, sexual dysfunction, body image concerns, and fertility status affect their confidence in being both physically and emotionally intimate. Despite this evidence, limited research has investigated the influence of psychosocial and interpersonal factors on sexual health outcomes reported by this group. This constitutes a significant gap in the provision of comprehensive sexual health care for adolescent- and young adult–onset cancer survivors, especially since greater emphasis has been recently placed on the biopsychosocial model of sexuality and dyadic approaches to intervention and treatment. In comparison to other cancer types, the incidence of colorectal cancer (CRC) has been increasing at an alarming rate for the adolescent and young adult group. Patients with early-onset CRC experience elevated rates of sexual dysfunction, psychological distress, and social and physical burden, often resulting from issues with bowel control, incontinence, and body image. Objective This study uses an explanatory sequential mixed methods approach to (1) characterize sexual function, sexual distress, dyadic coping, infertility-related distress, relationship and mental health outcomes of adolescent and young adult CRC survivors within the first 5 years post diagnosis and their partners; (2) examine the reciprocal influence of sexual function and dyadic coping behaviors on sexual distress; and (3) identify interpersonal or couple characteristics associated with coping with sexual dysfunction and its associated distress. Methods Participating couples (n=60) will complete a quantitative web-based survey investigating sexual function, sexual distress, dyadic coping, infertility-related distress, emotional functioning, relationship satisfaction, and body image (cancer survivors only). A subset of 20 couples will participate in an in-depth dyadic interview with 2 members of the research team to further explore couple-based strategies implemented to cope with cancer-related sexual dysfunction and distress. Results The study received institutional review board approval. Recruitment and enrollment of couples began in July 2022. Conclusions Results will provide a deeper understanding of the challenges couples experience as they navigate sexual intimacy after CRC treatment by highlighting the role of interpersonal processes. These findings will inform a dyadic intervention for young couples at risk of greater sexual distress in the aftermath of CRC. International Registered Report Identifier (IRRID) DERR1-10.2196/41831