Brees easily his extended his NFL-record streak of games with at least one TD pass to 49, finishing 27-for-37 for 377 yards and an interception.
Lance Moore racked up 121 receiving yards on nine catches as New Orleans (2-4) won a second straight game.
The Buccaneers (2-4) were led by Vincent Jackson, who made seven grabs for a franchise-record 216 yards and a touchdown.
Josh Freeman rolled up 420 passing yards and three scores on 24-for-42 efficiency for Tampa Bay.
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