Oxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for ATP production. The reliance on each varies across tissues and cell states, and can influence susceptibility to disease. At present, the full set of molecular mechanisms governing the relative expression and balance of these two pathways is unknown. Here, we focus on genes whose loss leads to an increase in OXPHOS activity. Unexpectedly, this class of genes is enriched for components of the pre-mRNA splicing machinery, in particular for subunits of the U1 snRNP. Among them, we show that LUC7L2 represses OXPHOS and promotes glycolysis by multiple mechanisms, including (1) splicing of the glycolytic enzyme PFKM to suppress glycogen synthesis, (2) splicing of the cystine/glutamate antiporter SLC7A11 (xCT) to suppress glutamate oxidation, and (3) secondary repression of mitochondrial respiratory supercomplex formation. Our results connect LUC7L2 expression and, more generally, the U1 snRNP to cellular energy metabolism. Display omitted •Expression of LUC7L2 and the U1 snRNP represses OXPHOS•Pre-mRNA splicing and expression of PFKM and SLC7A11 (xCT) requires LUC7L2•Loss of LUC7L2 and glycolysis promotes respiratory chain (super)complex assembly•LUC7 family members cross-regulate each other's expression Jourdain et al. report the identification of OXPHOS repressors, genes whose loss shifts metabolism from glycolysis to OXPHOS. Prominent in this set are members of the U1 snRNP, including LUC7L2. The authors show that loss of LUC7L2 leads to metabolic crossovers at PFKM and SLC7A11 (xCT), thereby impacting glycogen formation and glutamate oxidation.