Immunosuppression is a characteristic hallmark of renal cell carcinoma (RCC), with several complex immune defects, almost solely at the level of cell-mediated immune function, well evident even in patients at first diagnosis. The main circulating lymphocyte subsets and the total number of circulating dendritic cells were quantified in 47 RCC patients at diagnosis (T0), 12 h (T1), 24 h (T2) and 8 days following either radical nephrectomy or nephron-sparing surgery using flow cytometry. RCC patients presented, at baseline, (T0) a profound state of immunosuppression involving naïve T-cells, memory T-cells, CD16+ NK and total circulating dendritic cells, that worsened after 12 (T1) and 24 h (T2) from surgery, involving the majority of the analysed subsets; after 8 days (T3) from surgical removal of tumor, however, there was a return of all the analyzed parameters to the basal state. In conclusion, surgery causes transient but relevant immune suppression in RCC patients; even though, by day +8, this tends to return to baseline, immunostimulatory therapies could be considered in the peri-operative setting with the aim of reducing immunosuppression and, hopefully, also disease recurrence.