Purpose <p>This study investigated the associations between physical activity, sleep, and joint pain intensity with physical function and health-related quality of life (HrQoL) in people with multimorbidity.</p> Methods <p>A pre-specified cross-sectional study using baseline data from participants with multimorbidity in the MOBILZE trial. Outcomes were physical function (6-minute walk test) and HrQoL (EQ-5D-5&#xa0;L). Exposures were device-measured physical activity (min/week), joint pain intensity (0-100 visual analogue scale), device-measured sleep efficiency (%), and sleep quality (Modified Karolinska Sleep Questionnaire, 0–5 Likert scale). Separate and combined linear regression models were used to assess associations between exposures and outcomes.</p> Results <p>We included data from 227 participants. Physical activity was positively associated with physical function (β = 0.56&#xa0;m, 95% confidence intervals (CI) 0.39 to 0.73) and HrQoL (β = 0.00046, CI 0.000054 to 0.00087). Joint pain intensity was negatively associated with physical function (β = -0.90&#xa0;m, CI -1.61 to -0.19), but not quality of life. Poorer sleep quality was negatively associated with HrQoL (β = -0.037, CI -0.060 to -0.013), but not physical function. Sleep efficiency was not associated with either outcome. In the combined model, physical activity was not associated with HrQoL, while joint pain was.</p> Conclusions <p>Our exploratory findings among people with multimorbidity suggest that physical activity and joint pain are potentially clinically meaningful factors relating to physical function, while self-reported sleep quality may meaningfully relate to HrQoL. Clinicians may want to consider supporting patients with multimorbidity in managing their physical activity levels, joint pain, and sleep quality to improve health outcomes. Longitudinal studies and randomised controlled trials are needed to confirm these findings.</p>