Experimental evidence for the physiological effects of secondhand smoke (SHS) is limited although it affects millions of people globally and its prevalence is increasing, despite currently adopted anti-smoking measures. Also, scarce evidence suggests that the effects of SHS may be more pronounced in men. We conducted a randomized single-blind crossover study to investigate the sex-specific SHS effects in a controlled simulated bar/restaurant environment on gonadal and thyroid hormones, inflammatory cytokines, and vascular function. Twenty eight (women=14) non-smoking adults underwent a 1-hour exposure to moderate SHS and a 1-hour control trial. Serum and urine cotinine, gonadal and thyroid hormones, inflammatory cytokines, heart rate, and arterial blood pressure were assessed prior to exposure and immediately after in both trials. Results showed that testosterone (P=0.019) and progesterone (P<0.001) in men, and 17-estradiol (P=0.001) and progesterone (P<0.001) in women were significantly decreased following SHS. In men, SHS was accompanied by increased free thyroxine (P<0.001), triiodothyronine (P=0.020), and decreased triiodothyronine:free thyroxine ratio (P=0.033). In women, significant SHS-induced change was observed only in free thyroxine (P=0.010), with considerable sex variation in free thyroxine and triiodothyronine and a decrease in luteinizing hormone (P=0.026) and follicle-stimulating hormone (P<0.001). Following SHS, interleukin-1 beta (P=0.001) and systolic blood pressure (P=0.040) was increased in men but not women. It is concluded that a 1-hour SHS exposure at bar/restaurant levels is accompanied by decrements in gonadal hormones in both sexes and marked increases in thyroid hormone secretion, IL-1 production and systolic blood pressure in men.