Spent coffee grounds are rich in high-value compounds, such as saturate and unsaturated fatty acids, and polysaccharides. Therefore, this work investigated a cascade biorefinery to produce: i) biodiesel from coffee oils, ii) cellulose- and hemicellulose-derived fermentable sugars and iii) biomethane from the residual solid fraction after sugars extraction. Transesterification reached the best performances of 86% w/w of fatty acid methyl esters using 1:8 coffee oil/methanol ratio and 2% w/w of KOH as catalyst. The use of glycerol for the pretreatment of spent coffee grounds allowed the internal circulation of a process leftover from transesterification; thus, avoiding the use of clean water. In the best conditions, the total released fermentable sugars were about 40-50% (w/w) on dry weight basis. The low content of easily degradable compounds led to a low methane production of 50 LCH4/kgVS, indicating the need to search for better performing alternatives to close the biorefinery loop.