In his later years Manus was troubled by quarrels between his sons Calvagh and Hugh MacManus; in 1555 he was made prisoner by Calvagh, who deposed him from all authority in Tyrconnel, and he died in 1564.
Manus O'Donnell, though a fierce warrior, was hospitable and generous to the poor and the Church.
Manus was several times married.
1566), eldest son of Manus O'Donnell, in the course of his above-mentioned quarrel with his father and his half-brother Hugh, sought aid in Scotland from the MacDonnells, who assisted him in deposing Manus and securing the lordship of Tyrconnel for himself.
Hugh Roe O'Donnell (1572-1602), eldest son of Hugh MacManus O'Donnell, and grandson of Manus O'Donnell by his second marriage with Judith O'Neill, was the most celebrated member of his clan.