The Theory of Homeostasis posits that Subjective Well-being (SWB) is regulated by a dynamic biological mechanism, assisting to maintain a positive view of life. Further, the theory suggests that clinical depression is the loss of SWB due to the defeat of this homeostatic defence system. To test this hypothesis it was predicted that people who were diagnosed as clinically depressed with the Semi-structured Clinical Interview (SCID-1/NP) based on the DSM-IV-TR Axis 1 would have a Personal Well-being Index-Adult (PWI-A) score below the normative range (70–80% of scale maximum). Following ethical approval a sample of 146 men was obtained and each was assessed on the SCID-1/NP and on the PWI-A. Subjects diagnosed as having one of several pathologies such as post traumatic stress disorder, panic disorder, social phobia and specific phobia were found to score significantly lower on the PWI-A compared to participants who received no diagnosis. However, as the data did not discriminate between currently depressed and persons with other non-depressive psychopathologies, a Receiver Operating Characteristics (ROC) curve analysis was used to explore this data further. Results indicated that the PWI-A was significantly better than guessing in discriminating clinically depressed cases, but only just so. Therefore, while this research found support for the proposition that the loss of SWB indicated clinical depression, the PWI-A is not sufficiently specific for diagnosis, nor can it be concluded that all instances of depression is the failure of SWB.