Several studies have reported immune system alterations in depressed patients. Furthermore, correlations between some interleukins and specific depressive symptoms have been found, but results are ambiguous. It might be caused by heterogeneous patient population and concomitant administration of antidepressants. The aim of our study was to look at differences in the levels of soluble interleukin-2 receptor (sIL-2R) and tumor necrosis factor-alpha (TNFalpha) between currently depressed patients with first or recurrent episode of depression, patients in full remission and healthy controls. Secondly, we looked for correlations between sIL-2R and TNFalpha and different depressive symptoms. A total of 75 medication-free currently depressed patients (76% of females), 17 patients in the full remission phase of major depression (58.8% of females), and 55 healthy controls (58.2% of females) participated in this study. The results showed that the level of sIL-2R was significantly lower in depressed patients in remission phase compared to the healthy controls and subjects with recurrent depression. Drug-naļve patients with major depressive disorder with recurrent episode had higher levels of sIL-2R than previously treated or patients with the first episode. TNFalpha levels were higher in drug-naļve patients with major depressive disorder with recurrent episode compared with previously treated patients. Further analysis of patients revealed that sIL-2R was positively correlated with decreased activity and agitation. TNFalpha was associated with decreased activity and suicidality.