Aim:Low-intensity neuromuscular electrical stimulation was offered as a safe (non-traumatic) approach to prevent the loss of muscle mass, strength, and endurance in patients with severe chronic diseases and in spaceflight. However, the effects of this approach on various leg muscles are poorly investigated.Methods:This study assessed the efficiency of low-intensity (~10% of maximal voluntary contraction) electrical stimulation in preventing the negative effects of weekly disuse (dry immersion without and with daily stimulation) on the strength and aerobic performance of the ankle plantar flexors and knee extensors, mitochondrial function in permeabilized muscle fibers, and the proteomic (quantitative mass spectrometry-based analysis) and transcriptomic (RNA-sequencing) profiles of the soleus muscle and vastus lateralis muscle.Results:Application of electrical stimulation during dry immersion prevented a decrease in the maximal strength and a slight reduction in aerobic performance of knee extensors, as well as a decrease in maximal (intrinsic) ADP-stimulated mitochondrial respiration and changes in the expression of genes encoding mitochondrial, extracellular matrix, and membrane proteins in the vastus lateralis muscle. In contrast, for the ankle plantar flexors/soleus muscle, electrical stimulation had a positive effect only on maximal mitochondrial respiration, but accelerated the decline in the maximal strength and muscle fiber cross-sectional area, which appears to be related to the activation of inflammatory genes.Conclusion:The data obtained open up broad prospects for the use of low-intensity electrical stimulation to prevent the negative effects of disuse for ″mixed″ muscles, meanwhile, the optimization of the stimulation protocol is required for ″slow″ muscles.