Abstract Background Evidence on the association between obesity and suicide is mixed. However, the strength of obesity as a predictor of suicide may be reduced, because of the role of weight changes associated with mental disorders. We tested the hypothesis that both obesity and unexplained weight loss are related to elevated suicide risk. Methods A clinical examination with measurements of height, weight and self-reported unexplained weight loss was conducted at baseline for 18,784 men aged 40 to 69. Based on national mortality register data, 61 suicides were identified during the 38-year follow-up. Results The age-adjusted hazard ratio for suicide among obese versus normal weight men was 2.22 (95% CI 0.94 to 5.28). Additional adjustment for unexplained weight loss raised this ratio to 2.48 (95% CI 1.04 to 5.92). Unexplained weight loss was associated with a substantial excess risk of suicide irrespective of obesity (age-adjusted hazard ratio 5.38, 95% CI 2.31 to 12.50; age- and obesity-adjusted hazard ratio 5.58, 95% CI 2.37 to 13.13). Limitations Inability to take into account the effect of depression as a potential mediating mechanism. Conclusions This study provides evidence that both obesity and unexplained weight loss may be important predictors of suicide. Lack of adjustment for weight loss may suppress the observed association between obesity and suicide.