ObjectiveTo determine whether the comorbidity burden and co-existing comorbidities are cross-sectionally and/or longitudinally associated with pain and pain sensitization in a cohort study of people with hand OA.DesignWe examined whether comorbidity burden and individual comorbidities based on the self-administered Comorbidity Index (range: 0–42) at baseline were associated with pain outcomes at baseline and 3 years follow-up. Pain outcomes included hand and overall bodily pain (range: 0–10) as well as pressure pain thresholds at the tibialis anterior muscle (kg/cm2) and temporal summation (distal radioulnar joint) as measures of central pain sensitization. We performed linear regression analyses adjusted for age, sex, body mass index, physical exercise and education.ResultsWe included 300 and 196 participants in cross-sectional and longitudinal analyses, respectively. Using baseline data, the burden of comorbidities was associated with greater pain in hands (beta ​= ​0.61, 95% CI 0.37, 0.85) and overall body (beta ​= ​0.60, 95% CI 0.37, 0.87). Similar strength of associations was found between comorbidity burden (baseline) and follow-up pain. Among the individual comorbidities, back pain and depression were associated with nearly one unit higher pain score in hands and overall body at both baseline and follow-up. Only back pain was related to lower pressure pain thresholds at follow up (beta ​= ​−0.24, 95% CI −0.50, −0.001).ConclusionPeople with hand OA and greater comorbidity burden, co-existing back pain or depression reported greater pain severity than their counterparts, also 3 years later. These results acknowledge the relevance of accounting for comorbidities in the pain experience in people with hand OA.