This report presents a case of complicated and consistently failing weaning attempts in a male ICU patient admitted with respiratory failure. A systematic failure-to-wean analysis was performed but offered insufficient help in this case. Endocrinological evaluation showed a lowered total testosterone which was supplemented after other courses of action seemed exhausted. Interestingly, supplementation was followed by a sudden clinical improvement and successful weaning. Testosterone levels generally decrease as part of extensive hormonal alterations in critical illness and are inferred to contribute to the catabolic state frequently seen in critically ill men. Low testosterone values have been linked with weaning failure and multiple other adverse outcomes, but studies concerning the effects on weaning are few and not comprehensive. More research concerning testosterone replacement in the ICU is warranted, but the surprising effects of supplementation in this case suggest that analysis of testosterone levels and potential supplementation are valuable considerations in weaning failure. © 2018, Netherlands Society of Intensive Care. All rights reserved.