Wine lees from 11 different wineries pertaining to two denominations of origin in Spain (La Rioja and Ribera del Duero) have been characterized in this research by LC-MS/MS in high-resolution mode. For this purpose, the wine lees were separated into the liquid phase (imbibed wine from lees) and the solid residue, which was dried and subjected to solid-liquid extraction assisted by microwaves (dried lees). Both fractions were separately analyzed and the fractions from the 11 wineries compared to find similarity in their patterns. The statistical analysis enabled both differences and common aspects in the composition of imbibed wine from lees and dried lees from all wineries to be found. MS/MS tentative identification of representative compounds in each fraction revealed the varied composition of wine lees with special emphasis on flavonoids such as quercetin, myricetin, and malvidin 3-galactoside, identified in extracts of dried lees, or other compounds such as kaempferol 3-(2',3'-diacetylrhamnoside)-7″-rhamnoside, aminocaproic acid, and citric acid, exclusively identified in imbibed wine from lees. The adsorbent capacity of the solid residue justified the high concentration of phenolic compounds in the extracts from solid lees. The differences found in the composition of the two phases support the separated exploitation of them.