Abstract: Chronic illnesses often force people to reduce their participation in valued activities and interests such as work, leisure activities, hobbies, education, household duties and so forth. Despite empirical evidence suggesting that illness intrusiveness (lifestyle disruptions attributable to an illness and (or) its treatment that interfere with continued engagement in valued activities and interests) can significantly compromise quality of life and that individuals differ significantly in illness intrusiveness even under objectively similar conditions, research in this direction is rather scanty, especially in Nigeria. This study investigated the extent to which personality (neuroticism), duration of illness and socio-demographic factors would influence the perception of illness intrusiveness among patients with diabetes mellitus. Participants were 122 attendees of two General Hospitals in Ibadan, South-Western Nigeria, in treatment for diabetes mellitus. A structured questionnaire, consisting of standardized measure of illness intrusiveness, neuroticism and a section which measured socio-demographic variables was used to collect data. Resultsindicated that neuroticism was positively related to illness intrusiveness while age and duration of illness were negatively related to illness intrusiveness. Results also indicated that male patients reported significantly higher on illness intrusiveness than females, t (2,119) = 4.83; p<0.05. These findings were discussed and the need for further studies was highlighted. It was strongly recommended that individuals experiencing chronic illness should be helped and encouraged to engage in hobbies and valued activities as much as possible in order to reduce their perceived illness intrusiveness and enhance their quality of life.