Linoleic acid consumption has increased by orders of magnitude over the past century, eliciting an increasing awareness of and appreciation for its metabolites, particularly 4-hydroxynonenal (4-HNE). Elevated 4-HNE formation is causally implicated in myriad neurodegenerative, cardiovascular, autoimmune, and metabolic disorders. The purpose of this project was to identify the effect of 4-HNE on muscle cell mitochondrial bioenergetics. Our primary observation was that physiological levels of 4-HNE compromised muscle cell mitochondrial oxygen consumption, leading to reduced oxygen flux despite a substantial production of reactive oxygen species (ROS). Indeed, when viewed in light of the reduced oxygen consumption, the relative production of ROS with 4-HNE was even more pronounced. These findings could explain the significant reduction of cell viability demonstrated. In conclusion, this work joins the growing body of evidence suggesting a need to scrutinize dietary linoleic acid consumption.