Few efforts have been made to prospectively identify resources and obstacles outside work that may predict regained work ability and return to work when workers are on sick leave. This study investigates the association between partner relationships and sick leave. Our research questions were as follows: (i) What is the influence of sick leave, pain, stress and domestic strain on the quality of the dyadic partner relationship?, and (ii) What is the influence of the partner and social relationship on pain, stress, work ability, self-rated health and return to work? A cohort of female workers (n = 225) on long-term sick leave (>60 days), all in a partner relationship, at 6-month intervals completed a questionnaire based on the Quality of Dyadic Relationship (QDR) instrument, the Interview Schedule of Social Interaction (ISSI), the Work Ability Index (WAI) and the Copenhagen Psychosocial Questionnaire (COPSOQ). Univariate and multivariate analyses of baseline and prospective data were performed. The results showed that decreased partner relationship quality was related to having major responsibility for household work despite being on sick leave, having pain and having decreased social integration. Among younger individuals on sick leave, a reduction in the quality of the partner relationship was shown already at the first (6-month) follow-up, while among middle-aged women, such a reduction was seen only at the 12-month follow-up. No dimensions of partner relationship quality at baseline were related to dimensions of return to work, either as a resource or as an obstacle. Consequently, our results show that a good relationship does not keep the woman from returning to work. Having main responsibility for household work, which implies domestic strain while on sick leave, predicts lower partner relationship quality. The practical implications are that healthcare professionals treating women on sick leave should emphasize the importance of keeping a social network as well as making sufficient adjustments at home for the relationship quality to be safeguarded. Special attention should be given to the young woman on sick leave as being on sick leave seems to influence her partner relationship considerably.