Cumulus expansion and oocyte maturation are central processes in ovulation. Knowledge gained from rodent and other mammalian models has revealed some of the molecular pathways associated with these processes. However, the equivalent pathways in humans have not been thoroughly studied and remain unidentified.Compact cumulus cells (CCs) from germinal vesicle (GV) cumulus oocyte complexes (COC) were obtained from patients undergoing in-vitro maturation (IVM) procedures. Expanded CCs from metaphase 2 (M2) COC were obtained from patients undergoing IVF/ICSI. Global transcriptome profiles of the samples were obtained using state-of-the-art RNA sequencing techniques.We identified 1746 differentially expressed genes between compact and expanded CCs. Most of these genes were involved in cellular growth and proliferation, cellular movement, cell cycle, cell-to-cell signaling and interaction, extracellular matrix and steroidogenesis. Out of the differentially expressed genes, we found 89 long non-coding RNAs, of which 12 are encoded within introns of genes known to be involved in granulosa cell processes. This suggests that unique non-coding RNA transcripts may contribute to the regulation of cumulus expansion and oocyte maturation. Using global transcriptome sequencing, we were able to generate a library of genes regulated during cumulus expansion and oocyte maturation processes. Analysis of these genes allowed us to identify important new genes and non-coding RNAs potentially involved in COC maturation and cumulus expansion.These results may increase our understanding of the process of oocyte maturation and could ultimately improve the efficacy of IVM treatment.