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Histological evidence of skeletal muscle myopathy has been reported in ≈40–70% (Martin et al., 1985; Shenkman et al., 2019; Urbano-Marquez et al., 1995) of drinkers with a sustained (e.g., at least 3–4 years) history of alcohol consumption that approximates what has been defined as excessive alcohol consumption (i.e., more than 8 drinks per week for women and 15 drinks per week for men) by the 2015–2020 Dietary Guidelines for Americans (U.S. Department of Health and Human Services and U.S. Department of Agriculture 2015). This alcohol-induced myopathy manifests prominently in fast-twitch type muscles and results, at least in part, from a reduction in protein synthesis [as reviewed in (Kimball and Lang, 2018)]. As a result, both men and women who exhibit excessive drinking behavior as defined above have a reduction of muscle mass and the cross-section area (CSA) of such muscles (Shenkman et al., 2019; Thapaliya et al., 2014; Urbano-Marquez et al., 1995), with proximal muscle weakness being reported in ≈40% of these individuals (Estruch et al., 1998; Urbano-Marquez et al., 1995). This alcohol-induced myopathy in humans appears proportional to the total lifetime dose of alcohol consumed and may not be fully reversed in those who abstain from drinking alcohol (Estruch et al., 1998; Urbano-Marquez et al., 1995). Importantly, in other catabolic disease states, the loss of muscle and the accompanying muscle fatigue is directly proportional to survival (VanderVeen et al., 2018). Preclinical studies have also demonstrated similar changes in muscle mass and CSA in rodent models where alcohol consumption is prolonged (i.e., at least 6 weeks duration), and that this atrophy resulted, at least in part, in a reduction in mTOR (mechanistic target of rapamycin) complex 1 kinase activity that antagonizes basal and nutrient-stimulated synthesis of both myofibrillar and sarcoplasmic proteins (Lang, 2018; Lang et al., 1999; Thapaliya et al., 2014). While there has been considerable research into the mechanisms underlying the alcohol-induced loss of muscle mass (Kimball and Lang, 2018), there is a paucity of information pertaining to the effect of alcohol on skeletal muscle function. Many of the early studies in this regard revealed no or relatively isolated changes in specific parameters of contractility when skeletal muscles from chronic alcohol-fed rats and mice were stimulated via the sciatic nerve (Berk et al., 1975; Edmonds et al., 1987; Martyn and Munsat, 1980). However, in vitro incubation of muscle with ethanol decreased contractile function; although the concentrations used (1.8–2.5 g/dL) were certainly pharmacological and are far in excess of those typically reported in the blood of alcohol-consuming individuals (Martyn and Munsat, 1980; Taylor et al., 1992). Moreover, there are no studies that directly compare the effect of acute alcohol intoxication and chronic consumption on muscle function using the same experimental protocol. Hence, the purpose of the present study was to determine whether acute alcohol intoxication or chronic alcohol consumption decrease the intrinsic contractile function of fast-twitch skeletal muscle, independent of a change in nerve conduction, by assessing isometric and tetanic twitch force under basal conditions and after a fatiguing stimuli. To assess possible mechanisms for the observed alcohol-induced defects in contractile function, we also assessed the content of high-energy phosphates as well as the relative abundance of proteins in oxidative phosphorylation (OXPHOS) complexes 1–4 and selected contractile proteins under basal non-stimulated conditions.