A retired Marine general who fought in Iraq and Afghanistan, Mattis knows the region well and was a frequent visitor during his time heading up the US military's Central Command.
He was scheduled to meet the Crown Prince of Abu Dhabi, Mohammed bin Zayed Al Nahyan, and Defence Minister Mohammed Al Bawardi.
The Pentagon did not immediately release further details of the UAE trip, which comes after Mattis spent much of the week at summits in Brussels and Munich.
The UAE is seen as an important regional ally in the US-led coalition's fight against the Islamic State group in Iraq and Syria.
President Donald Trump in January spoke by telephone with Nahyan, committing to "further strengthen cooperation on fighting radical Islamic terrorism".
Gulf nations including the UAE are concerned about growing Iranian involvement in several regional conflicts, and Mattis, who has sounded a hawkish tone on Iran, has blasted Tehran for its "destabilising" influence.
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