Background/Aims: We examined in cigarette smokers whether cotinine was associated with depressive and/or anxiety disorders. Methods: Data were derived from 1,026 smoking adults with and without depressive and/or anxiety disorders participating in the Netherlands Study of Depression and Anxiety (NESDA). Depressive and anxiety disorders were ascertained with the DSM-IV Composite International Diagnostic Interview. Cigarette consumption was inquired about during an interview. Cotinine was assessed in plasma. Results: Currently depressed and/or anxious smokers (n = 692) reported smoking a higher number of cigarettes per day (CPD) than smokers with a remitted disorder (n = 190) and smokers with no lifetime disorder (n = 144). After controlling for CPD and other covariates, depressed and/or anxious smokers had lower cotinine levels compared to smokers with no lifetime disorder (B = -56.0, p = 0.001). In the full regression model, CPD was positively associated with cotinine levels, whereas current depression and/or anxiety and high body mass index were inversely associated with cotinine. Conclusion: After considering CPD, the presence of current depressive and/or anxiety disorders was associated with lower cotinine levels, which may point to a different smoking topography or a faster cotinine metabolism in individuals with affective disorders. The latter could help to explain the higher number of cigarettes smoked and poorer cessation rates among depressed or anxious patients. © 2014 S. Karger AG, Basel.