Background Low circulating testosterone and reduced sexual activity are common in men with obstructive sleep apnea. Objectives To evaluate the effect of an interdisciplinary weight loss and lifestyle intervention on circulating testosterone concentrations and, secondarily, on scores on the intimate relationships and sexual activity subdomain of the Functional Outcomes of Sleep Questionnaire (FOSQ). Methods Eighty-nine men were assigned to either usual care (n = 49) or an 8-week interdisciplinary intervention (n = 40). Assessments were conducted at baseline, at the end of the intervention (8 weeks), and 6 months post-intervention. Plasma testosterone was measured by chemiluminescence immunoassay. Sexual activity was assessed using the intimate relationships and sexual activity subdomain of the FOSQ. Sleep parameters and body weight and composition were also evaluated. Results Compared with the control group, higher plasma testosterone concentrations were observed in the intervention group at 8 weeks (between-group difference 77.6 [95% CI 4.2 to 150.1] ng/dL; p = 0.042) and at 6 months (between-group difference 90.4 [95% CI 11.7 to 169.0] ng/dL; p = 0.027). Scores on the FOSQ intimate relationships and sexual activity subdomain increased in the intervention group both at 8 weeks (between-group difference 1.0 [95% CI 0.5 to 1.5]; p = 0.004) and 6 months (between-group difference 0.8 [95% CI 0.2 to 1.3]; p = 0.003) compared with controls. Changes in testosterone and FOSQ-derived sexual activity scores correlated with favorable changes in sleep quality, body weight and body composition, particularly from baseline to 6 months and from 8 weeks to 6 months (all p < 0.05). Conclusions In men with overweight or obesity and moderate to severe obstructive sleep apnea, an interdisciplinary weight loss and lifestyle intervention increased circulating testosterone concentrations compared with usual care. Improvements were also observed in scores on the intimate relationships and sexual activity subdomain of the FOSQ; however, these findings should be considered exploratory because this subdomain does not assess erectile function, libido, hypogonadal symptoms, or validated multidimensional domains of male sexual function. Further studies using comprehensive endocrine profiling and validated male sexual function instruments are warranted.