Substitute Ryan Leonard scored four minutes after coming on as a substitute to earn Southend a late victory which takes them up to fifth in the table.
Leonard headed Michael Timlin's cross past new Oxford keeper Luke McCormick, who was playing his first Football League game since being jailed in 2008.
McCormick, signed from Truro City on deadline day, was barracked by the crowd but had little to do.
His opposite number Paul Smith twice denied Alfie Potter in the first half.
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