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Our objective was to investigate the psychobiological impact associated with resistance to further weight loss in obese men. Anthropometric and body composition measurements, resting metabolic rate (RMR) measurement, appetite sensation markers, and three questionnaires [Short Form-36 Health Survey (SF-36), Three-Factor Eating Questionnaire (TFEQ), and Beck Depression Inventory (BDI)] were assessed at baseline and after 1 month of body weight loss plateau induced by a supervised diet and exercise clinical intervention in 11 obese men. The weight loss plateau corresponded to 11.2% of initial body weight (93.9% from fat stores). However, this amount of weight loss induced a significant decrease in RMR (P <.05) and a significant increase in hunger (P <.05) and desire to eat (P <.05). Using the SF-36 Health Survey, physical and mental health were shown to be unchanged at plateau as compared to baseline. The TFEQ showed that cognitive dietary restraint increased (P <.001) compared to baseline. Finally, depression risk as measured by the BDI significantly increased at plateau (P <.01) compared to baseline. Weight loss until resistance to further weight loss may be detrimental for some psychobiological variables including depression, which emphasizes the relevance of caution and reasonable objectives when prescribing a weight reduction program for obese individuals.