Objectives The aim of this study was to investigate the relationship between suicidal behavior and chronobiological thyroid axis activity in depressed patients. Methods The serum levels of TSH, were evaluated before and after 8 AM and 11 PM TRH challenges, on the same day, in 230 medication-free DSM-IV euthyroid major depressed inpatients and 50 healthy hospitalized controls. Results Compared to controls: 1) patients with a recent suicide attempt (n = 71) showed lower TSH response to TRH (ΔTSH) at 11 PM, lower ΔΔTSH values (differences between 11PM-ΔTSH and 8AM-ΔTSH) (p Conclusions Our results suggest that in patients without a suicide attempt history increased hypothalamic TRH stimulation (as evidenced by reduced TSH responses to TRH) might be a compensatory mechanism. In patients with a suicide history this compensatory mechanism is not effective. In patients with a recent suicide attempt the evening TSH blunting, associated with reduced FT4 levels, might be indicative of a decreased central TRH activity leading to a reduction in the TSH resynthesis in the thyrotrophs during the day after the morning challenge.