Partial oxygen restriction in muscles during exercise, known as blood flow restriction (BFR), has been applied as alternative strategy to reproduce the effects of conventional high-load intensity training (HI) while training with low-loads (LI). Saliva may serve as a reliable tool for understanding the biological pathways involved in both protocols. This intervention and cross-over study evaluated the metabolic responses and the salivary protein profile before and after two different resistance training protocols. Ten participants were selected and underwent to training with LI (30%1RM – one repetition maximum) plus BFR vs. HI (70%1RM) without BFR, at 48h-interval. Stimulated saliva was collected before and immediately after the sessions, while breath-by-breath oxygen uptake (VO2) was measured during and after each session. Arterial blood samples for lactate concentration measurement (in EqO2[La]) were taken at 1st minute of resting between each exercise of the protocols. For HI, there was an increase in two actin cytoplasmic isoforms and two immunoglobulin isoforms and a decrease of six hemoglobin isoforms. For BFR, there was an increase in two hemoglobin isoforms, and the same immunoglobulin isoforms (t-test, p < 0.05). No differences were significant between HI and LI+BRF training regarding the total energy demand (in mlO2), absolute oxygen values (mlO2) for oxidative response (VO2ON), glycolytic (EqO2[La]), and oxygen debt (VO2OFF) (p>0.05). Both HI and LI+BFR protocols modulated immune system activity and exhibited divergent hemoglobin patterns. While HI training predominantly upregulated proteins associated with energy metabolism and muscle remodeling, BFR training revealed a proteomic signature suggestive of neuroprotective effects.