Background Functioning and quality of life are impaired in bipolar patients. Methods Collaborative Care (CC) is a multi-component intervention, provided by a multidisciplinary team, in which a nurse-care manager plays a central role. Effects on functioning and quality of life were tested in a clinical trial. We also investigated the mediating role of depression severity on these outcome variables. Results Patients randomized to CC showed more improvement in overall functioning compared to patients in the control group who obtained care as usual (CAU), with a small effect size (ES=0.3, z=-2.5, p=0.01). In the domains of autonomy and leisure time, a medium effect was found in favor of CC (autonomy: ES=0.5, z=-2.9, p=0.004; leisure-time: ES=0.4, z=-2.4, p=0.02). No differences between conditions were found in the other domains of functioning. Concerning quality of life, patients in CC improved more in the domain physical health (ES=0.4, z=2.5, p=0.01), if compared to CAU. No differences were found in overall quality of life. Half of the effects on functioning are mediated through the effects of CC on depression severity. Limitations At baseline, differences on the main outcomes existed between conditions. Two teams stopped participation in the experimental condition after randomization. Sample size was limited. Conclusion Besides effects on depressive symptoms, CC seems to have direct beneficial effects on both level of functioning and aspects of quality of life.