Bodyweight gain is a common side effect of treatment with antidepressive drugs; however, little is known about the mechanisms behind this weight gain. Genetic differences may contribute to the susceptibility for bodyweight gain during antidepressive treatment. The objective of this study was to examine the association of antidepressive-drug-induced bodyweight gain with polymorphisms in genes within the serotonin or catecholamine systems. Participants (N = 165) were selected from the Danish Psychiatric Central Research Register from June 2005 through May 2007 as patients with a diagnosis of a single depressive episode and who were under antidepressive treatment. Weight gainers were identified based on rating with the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Polymorphisms in catechol-O-methyltransferase, tryptophan hydroxylase (TPH1), serotonin receptor 2C (HTR2C) and serotonin transporter (SLC6A4) genes were identified and associated with bodyweight gain during treatment. The AG genotype of catechol-O-methyltransferase rs4680 and the AA genotype of TPH1 rs18532 were significantly associated with bodyweight gain during antidepressive treatment, when adjusted for age and sex. These new findings may aid the understanding of susceptibility to side effects such as weight gain during clinical antidepressive treatment.