The lead proved short-lived as Leicester winger Demarai Gray punished slack Southampton defending to rifle home the equaliser and the sending-off of Saints midfielder Pierre Hojbjerg in the 77th minute proved pivotal.
Hojbjerg's foolish dive and subsequent dismissal for his second yellow card handed the initiative to the visitors and Maguire sent a low shot into the bottom corner for the winning goal in stoppage time.
(Reporting by Philip O'Connor, editing by Ed Osmond)
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