The Spanish name Manolo is a familiar or diminutive form of Manuel. Manuel itself has a fascinating religious origin, tracing back to the Hebrew phrase 'ˁimmanu ˀel' (עִמָּנוּ אֵל) meaning 'God (is) with us'. This Hebrew phrase was borrowed into Greek as 'emmanouel' (ἐμμανουήλ), which then passed into Latin as 'emmanuel'. The Spanish form Manuel developed from this Latin version, and Manolo emerged as an affectionate nickname for Manuel, following a common Spanish pattern of creating diminutives.

The most directly related Spanish word is Manuel, which is the full form of the name from which Manolo is derived. This pattern of creating nicknames by modifying the original name (like adding -olo) is common in Spanish - similar to how Roberto becomes Berto or Francisco becomes Paco.

English speakers might recognize the connection to the name Emmanuel or Manuel, which share the same Hebrew origins meaning 'God is with us'. The name Emmanuel is particularly well-known in English-speaking countries through its use in Christian contexts, especially during the Christmas season, where it appears in carols and religious texts referring to Jesus Christ.