The authors agree that this surname derives from the Germanic given name Manfredo, documented in Lombard texts of the 8th century under the forms Magnifredus and Mahnifredo, and from the end of the 9th century in the Frankish forms Mainfredus and Manfredus. It is compounded from the elements magin- or main- ("power, strength") and frithu- ("peace"), with the sense of "power of peace", analogous in meaning to Federico.

A. Bongioanni notes that the name was frequent among the marquises of Saluzzo —the mother of King Manfredi was of this family— and documents derived Piedmontese surnames such as Manfredi, Manfredini and Manfredoni. The surname is found throughout Italy, with altered forms of greater presence in Lombardy and Emilia-Romagna. The shortened variants are concentrated in the areas of Veneto, Lombardy and the Romagna; Manfré predominates in Sicily, while Manfra and Manfriello are proper to the Naples area. Forms are further recorded in Piedmont and in Friuli-Venezia Giulia.