The Black Cats, hoping to close the gap on the chasing pack, had no answer to David Nugent's match-winning 36th minute header.
Sunderland had most of the play but were again let down by poor distribution and finishing and defeat was a bitter blow for another 30,000 plus crowd.
Preston were close to a first minute lead, Nugent taking on Stan Varga only to curl a measured shot from 18 yards just past the post.
Sunderland went even closer from a well-worked move. Dwight Yorke and Grant Leadbitter combined to set up David Connolly, who was denied the breakthrough by a fine save from Carlo Nash.
Yorke was too slow to take advantage of a shrewd flick by Leadbitter, his close-range angled drive blocked for a corner.
Sunderland's makeshift defence was further disrupted in the 16th minute when skipper Steve Caldwell limped off with a knee injury. Nyron Nosworthy, who began the game in the unusual position of left-back, switched to central defence with Lewin Nyatanga slotting in a full-back.
But the Black Cats, who had been in control without seriously the Preston defence, were rocked in the 36th minute. Brett Ormerod did well to keep the ball in play from the byline and with the home defence in complete disarray, Nugent had the simple task of nodding home from close range for his eighth goal of the season.
Stung into action, Sunderland huffed and puffed, but it was not until the introduction of Stephen Elliott for an ineffective Yorke for the start of the second half was there any improvement.
Nash saved a snap shot from Connolly and an overhead kick from Daryl Murphy whistled over the bar with the Preston defence under pressure for the first time.
Preston, however, continued to look dangerous on the break with Matt Hill galloping down the left flank only to shoot into the sidenetting.
Keane's last throw of the dice was to haul off Ross Wallace and send on Chris Brown in the 67th minute, but it was Liam Miller who tested Nash with a stinging drive.
Murphy fired across the face of goal and Brown twice came close to scoring with spectacular overhead kicks, but it just wasn't to be for a home side down to the bare bones in terms of fit players.
Preston always looked capable of adding to their lead on the break, soaking up the pressure to remain in second place in the Championship table.