Oocyte in vitro maturation (IVM) is an ART that involves the maturation of cumulus cell-enclosed oocytes (COCs) that are then capable of fertilization, implantation, and fetal development. We have recently shown that the EGF-like peptide signalling cascade, essential to oocyte maturation and ovulation in vivo, is perturbed in mouse COCs undergoing IVM when matured with the common additives follicle stimulating hormone (FSH) and/or epidermal growth factor (EGF), and that supplementation of IVM with EGF-like peptides amphiregulin or epiregulin improves oocyte developmental competence. Here we aimed to determine whether EGF-like peptides alter COC metabolism, resulting in increased oocyte developmental competence. Immature 129/Sv mouse COCs underwent IVM in the presence of FSH, EGF, amphiregulin, epiregulin, betacellulin, or no treatment (control). Epiregulin supplementation significantly increased intra-oocyte FAD++ compared to control and significantly increased the REDOX ratio compared to FSH and control (p<0.05). Amphiregulin and epiregulin significantly (p<0.05) increased the proportion of J-aggregates (from JC-1) in oocyte mitochondria compared to control, FSH or EGF, and this coupled with FAD++ and REDOX measures indicates greater mitochondrial activity. COC glucose consumption and lactate production were significantly lower in the control group (p<0.001), however, there were no differences between COCs treated with FSH, EGF and EGF-like peptides. COCs matured with EGF or EGF-like peptides exhibited significantly higher mRNA expression of the hexosamine biosynthesis pathway (HBP) rate-limiting enzyme gene Gfpt2, Has2 expression, and global β-O-linked glycosylation of proteins, compared to control or FSH (p<0.05), suggesting greater stimulation of HBP activity. In conclusion, findings from this study suggest that (i) EGF-like peptides, particularly epiregulin, induce more oocyte mitochondrial activity than EGF or FSH, possibly yielding more ATP production and (ii) EGF-like peptides and EGF induce greater activity of the HBP, enabling more hyaluronic acid synthesis and protein β-O-linked glycosylation, an important post-translational modification of proteins that regulates their activity.