The purpose of this study was to examine the acute immune response (circulating levels of leukocytes, cytokines and adipocytokines) to maximal resistance (MAX, 15 × 1RM) and hypertrophic resistance (HYP, 5 × 10RM) exercise bouts. Twelve healthy men (age = 28.2 ± 3.5 years, weight = 78.6 ± 10.4 kg, height 178.8 ± 5.0 cm, fat percentage = 16.5 ± 3.5 %) participated in the study. Blood was sampled before, immediately after and 15 and 30 min after exercise. Leukocytes (WBC) significantly increased immediately after HYP (p < 0.01), whereas in MAX, increases in WBC became significant after 30 min (p < 0.05). Lymphocytes increased only after HYP (p < 0.001), while MAX induced lymphopenia during recovery (p < 0.01). Monocyte chemoattractant protein-1 (MCP-1) decreased (p < 0.05) and interleukin-1 receptor antagonist (IL-1ra) increased after HYP, which were not observed after MAX. Adipsin and resistin decreased after both exercise bouts (p < 0.05), which suggest that heavy resistance exercise is at least transiently beneficial for adipocytokine profile. Immediate mechanical stress seemed similar as no differences in myoglobin response were observed. The higher magnitude of metabolic demand reflected in higher lactate response in HYP could be the reason for the significantly high responses in WBC, IL-1ra and decrease in MCP-1.