Background  Little is known about peoples’ self‐management experiences and their desires or expectations to engage in self‐management. As such, there is little understanding about individuals’ perceived cues and barriers to engagement in self‐management, particularly in people affected by cancer.Objective  To understand cues and barriers to people’s engagement in self‐management during chemotherapy treatment for colorectal cancer.Design  Secondary analysis of qualitative data from mixed methods, longitudinal study.Setting and participants  Eleven participants undergoing treatment for colorectal cancer. Semi‐structured interviews were conducted twice with each participant, at the start and end of a 6‐month course of chemotherapy treatment in a Scottish cancer centre.Results  Cues and barriers to engagement in self‐management appeared to stem from perceptions of the impact and associated severity of side effects experiences as well as the perceptions about the efficacy of chosen self‐management activities and perceptions of control in minimizing the consequences of cancer treatment. Severe, episodic or unexpected side effects coupled with perceptions of uncertainty, lack of control and lack of adequate preparation to engage in self‐management were identified as key barriers to engagement.Discussion and conclusion  Participants’ reflection on, or appraisal of, their treatment‐related experiences and personal abilities, confidence and preferences to manage the impact of these shaped their subsequent engagement in self‐management. The findings highlight the importance of understanding individual’s self‐management experiences, perceptions, preferences, priorities and needs to help support, prepare and enable them to feel capable and confident to engage actively and effectively in self‐management.