This study attempts to shed light on the efficacy of the solvent 2-methyloxolane (2-MeOx) as an alternative for hexane in defatting spent coffee grounds (SCG). Higher lipid yields were obtained with the bio-based solvent dry 2-MeOx (13.67%) and water-saturated 2-MeOx (15.84%) compared to hexane oil yield, which is of petroleum origin and is a known neurotoxin. Palmitic acid and linoleic acid were the principal fatty acids identified. The fatty acid profile of coffee oils obtained with hexane, dry 2-MeOx and aqueous 2-MeOx were similar. Lipid hydrolysis was observed in oils extracted with 2-MeOx, which warrants further investigation. The residual caffeine content in the defatted SCG was highest when hexane was used highlighting better solubility of methylxanthine compounds in the solvent 2-MeOx.