Study objectives High doses of short-term testosterone have been shown to acutely worsen sleep-disordered breathing in men with obstructive sleep apnoea (OSA). The effects of lower, nearconventional doses of testosterone in obese men with OSA may differ over the longer term but have not been systematically studied. We assessed sleep and breathing effects of near-conventional testosterone treatment as an adjunct to weight loss in obese men with severe OSA. Design An 18-week randomized, double-blind, placebo-controlled, parallel group trial in 67 men. Interventions All subjects were placed on a hypocaloric diet and then received intramuscular injections of 1000 mg testosterone undecanoate or placebo at 0, 6 and 12 weeks. Measurements and Results Sleep and breathing were measured by nocturnal polysomnography at 0, 7 and 18 weeks. Testosterone, compared to placebo, worsened the oxygen desaturation index (ODI) by 10.3 events/h (95%CI, 0.8-19.8 events/h; P = 0.03) and nocturnal hypoxaemia (sleep time with oxygen saturation <90%, SpO2T90%) by 6.1% (95%CI, 1.5 -10.6; P = 0.01) at 7 weeks. Testosterone therapy did not alter ODI (4.5, -5.4 to 14.4 events/h; P = 0.36) or SpO2T90% at 18 weeks (2.9, -1.9-7.7%; P = 0.23) compared to placebo. The testosterone treatment effects on ODI and SpO2T90% were not influenced by baseline testosterone concentrations (testosterone by treatment interactions, all P > 0.35). Blood testosterone concentrations did not correlate with ODI or SpO2T90% (all P > 0.19). Conclusions Testosterone therapy in obese men with severe OSA mildly worsens sleep-disordered breathing in a time-limited manner, irrespective of initial testosterone concentrations. This time-dependency was not related to testosterone concentrations.