Lira, FS, Conrado de Freitas, M, Gerosa-Neto, J, Cholewa, JM, and Rossi, FE. Comparison between full-body vs. split-body resistance exercise on the brain-derived neurotrophic factor immunometabolic response. J Strength Cond Res 34(11): 3094-3102, 2020-Intense aerobic exercise seems to increase serum concentrations of brain-derived neurotrophic factor (BDNF) in conjunction with increasing lactate; however, less is known about the BDNF response to differing resistance exercise protocols. We hypothesized that full-body (FB) resistance exercise will elicit a greater increase in serum BDNF and lactate compared with split-body resistance exercise. Twelve recreationally resistance-trained men (age = 25.3 ± 5.9 years) performed 3 randomized trials of 18 sets of exercise: upper-body (UB), lower-body (LB), and FB conditions. Serum BDNF levels were assessed at rest, immediately Post-exercise, Post-1 hour, and Post-2 hours during recovery. Lactate concentration was evaluated at rest, after 9 sets, Post-exercise, Post-5, Post-10, and Post-30 minutes during recovery. In addition, interleukin (IL-6 and IL-10) and the IL-6/IL-10 ratio were calculated. Lactate concentration and total volume were greater in the FB condition compared with LB and UB (p < 0.05). For BDNF, effect sizes were largest in the LB (1.4), followed by the FB (0.75), and moderate to UB (0.33), although no significant differences were observed between conditions. There was a statistically significant relationship between lactate and BDNF only for LB condition (rho = 0.72; p = 0.013). There were a greater IL-10 Post-1 hour for FB condition compared with UB and LB (p < 0.001), and lower IL-6/IL-10 ratio in FB compared with UB (p < 0.001). Lower body induced a great BDNF response, and FB resistance exercise elicited a greater increase of serum cytokines than UB in trained men. We speculate that the volume of work performed by larger muscles has a larger influence on BDNF than overall volume.