Objective To detect the levels of cytokines in first-episode depressant patients and the influence on the levels of cytokines after the treatment with sertraline and venlafaxin. Methods The levels of IL-2,IL-6,TNF-α and IL-10 were measured in 80 first-episode depressant patients and 40 healthy control subjects. 80first-episode depressant patients were divided into two groups which were treated by sertraline and venlafaxin respectively. The levels of the same items were measured after 6-week treatment with sertraline and venlafaxin. All data were statistically analyzed by SPSS. Results The levels of IL-2,IL-6,TNF-α in 80 first-episode depressant patients were significantly higher than that in control group( IL-2:(6.79 ± 2.89 )pg/ml vs (4.06 ± 2.05 )pg/ml;IL-6:(10.12 ±4.52)pg/ml vs (6.04 ± 1.79) pg/ml;TNF-α: ( 14.81 ±4.38) pg/ml vs ( 10.69±2.54) pg/ml)(P＜0.05). The level of IL-6 after treatment by sertraline and venlafaxin was lower than that before treatment.There were no significant difference of the levels of IL-2,TNF-α, IL-10 before and after treatment. No significant difference of the levels of cytokines were observed between the two groups which were treated by sertraline and venlafaxin. Conclusions There are some changes of the levels of cytokines in first-episode depressant patients, which might be corrected by the treatment with sertraline and venlafaxin. Sertraline and venlafaxin might have the same mechanisms to cytokines.