Objective The aim of this study was to examine the association of depressive symptoms with asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Patients with chronic hepatitis C infection were examined during interferon- (IFN-) treatment, which is often associated with treatment-induced depression. The associations between IFN--induced depressive symptoms with ADMA and SDMA levels were prospectively investigated until 3 months after treatment. Methods Psychiatric and biological assessments were obtained at six different time points: before, during (at 1, 3, 6, and 9 months), and after the end of IFN- treatment. Results During IFN- treatment, 22 (53.7%) patients fulfilled the criteria for a treatment-related depressive disorder at least once during treatment. The increase in ADMA levels from baseline (depression group: 0.63 [0.08] M, no depression group: 0.69 [0.08] M) in response to IFN- treatment was considerably higher in patients with IFN- treatment-induced depressive episodes compared with patients without treatment-induced depressive episodes (3 months after the start of treatment: depression group: 0.72 [0.08] M, no depression group: 0.72 [0.11] M; ADMA: repeated-measure design analysis of variance [time x depression]: F(5,151) = 2.446, p = .036). The increase in SDMA was not associated with treatment-induced depression. Conclusions Depression in response to IFN- treatment is associated with elevated ADMA levels. These findings are relevant to nitric oxide-related biological pathways linking depression to increased cardiovascular disease risk. Future studies are needed to clarify the role of serotonin in these pathways and may lead to preventative treatment strategies.