We aimed to evaluate the effects of low-load resistance exercise with blood flow restriction (BFR) on high-energy phosphate metabolism, intracellular pH, and oxygenation level in the skeletal muscle. Seven males performed low-load ankle plantar flexion exercise (120 repetitions, 30% of one-repetition maximum) with and without BFR (130% of systolic blood pressure) inside a magnetic resonance device. Inorganic phosphate (Pi)-to-phosphocreatine (PCr) ratio, intracellular pH, and tissue oxygenation index (TOI) in the medial gastrocnemius were determined using 31P-magnetic resonance spectroscopy and near-infrared spectroscopy before and during exercise. The Pi-to-PCr ratio significantly increased during exercise in both conditions, with the BFR-condition values significantly exceeding the control-condition values. The BFR and control conditions showed significantly decreased intracellular pH during exercise, with the BFR-condition values being significantly lower than the control-condition values. The TOI significantly decreased during both exercises, but the decreases in the BFR condition were significantly greater than those observed in the control condition. Low-load BFR exercise places greater metabolic stress (greater PCr depletion, lower intracellular pH, and lower oxygenation level) on an exercising muscle than low-load non-restricted exercise.