OBJECTIVES: To investigate whether that nicotine concentration represented by the degree of smoking dependence variably influence the rate and severity of depressive symptoms. METHODS: Cross-sectional, analytical study, involving 300 medical students selected by random sampling techniques were asked to complete a questionnaire contains three parts: demographic information, Beck Depression Inventory with cutoff point for depression is 17 and the Fagerstrom Test for Nicotine dependence with cutoff point for severe dependence is five. RESULTS: A total of 233 medical students completed the questionnaire; their mean age was (21.38 +/- 1.74). The rate of smoking was 22.7% while that of depression was 32.2%. Low dependent smokers in contrast to other groups of smokers and non-smokers display the lowest rate of depressive symptoms (15%), while the highest rate recorded among severely dependent smokers (71.4%, p = 0.0001). After adjustment of other risk factors, regression analysis reveal that severe dependent smokers associated with 12.5 odds of depressive symptoms than non-smokers (p = 0.0001, C.I. 4.10-38.29). CONCLUSION: In comparison with light and moderate smokers, heavy smokers demonstrate higher risk of depressive symptoms in medical students.