The milk whey remaining at the end of the cheese-making process is the main by-product of the dairy industries and it is currently used as a source of high added-value compounds by the food and pharmaceutical industries. The aim of this research was to study the effects of the season on the residual whey characteristics in the Parmigiano Reggiano cheese-making process. Over two years, a total of 288 cheese-making trials of Parmigiano Reggiano PDO (Protected Designation of Origin) cheese were performed in three commercial cheese factories and, in each trial, a sample of the vat milk (V-milk) and of the residual whey (C-whey) were collected. The C-whey values of dry matter and non-fat matter were higher in winter and autumn than in spring and summer. Moreover, the C-whey fat and crude protein contents were also higher in autumn (0.52 and 0.89 g/100 g, respectively) and lower in spring (0.44 and 0.83 g/100 g, respectively) and summer (0.46 and 0.84 g/100 g, respectively). Furthermore, crude whey protein resulted to be the major fraction of crude protein (97.96%). Crude whey protein and true whey protein were higher in autumn and lower in spring and summer and their values mainly depended on milk whey protein. Finally, the C-whey average contents of phosphorus and magnesium were higher in autumn and winter than in summer.