Any remaining hope Reading had of beating the drop appeared to be extinguished as Nigel Adkins' first home match at the helm ended in a 2-0 defeat to former club Southampton.
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Another inspired performance from Jay Rodriguez proved the difference at the Madejski Stadium as Saints ran out comfortable 2-0 winners, condemning the bottom-placed Royals to a seventh successive defeat.
The result leaves the Berkshire side seven points adrift of safety with just six matches remaining, making an immediate return to the Championship increasingly likely.
Talk in the build-up was about Adkins exacting revenge on the club that so harshly disposed of his services 78 days ago, despite having led Saints to back-to-back promotions.
However, after weathering the Royals' early pressure, it was successor Mauricio Pochettino that enjoyed the spoils as Saints won a third successive Premier League match for the first time since 2003.
Rodriguez again proved the difference for Saints, bundling home the opener before rattling the crossbar as half-time approached.
The 23-year-old then turned provider in the second half as he sent a perfectly-weight ball to substitute Adam Lallana, who slotted home to push Adkins closer to the drop.
The Reading boss made five changes from side that lost 4-1 at Arsenal for this match, ahead of which he received applause from those in both blue and red.
It was a touching reception for the former Saints boss, who, after shaking hands with his successor, saw his side enjoy the brighter start.
One-time Southampton loanee Danny Guthrie produced the first chance of the afternoon, with his deep free-kick headed over by Sean Morrison.
It was one of few chances of note in a tentative opening 20 minutes due to a combination of poor decision-making and sturdy defending.
The visitors were looking more disjointed than in their recent impressive performances and were fortunate not to fall behind.
As Reading upped the ante Adam Le Fondre was guilty of wasting a decent close-range effort, blazing over after Saints' laughable attempts to clear a free-kick saw the ball land kindly for him.
Adkins' side returned to the attack immediately and felt they should have had a penalty, only for referee Mike Jones to waved away the appeals that followed Jos Hooiveld's challenge on Hal Robson-Kanu.
The hosts were further frustrated soon after, with Artur Boruc reacting superbly to deny a goalbound Adrian Mariappa header down low to his right.
That chance appeared to act as a wake-up call for Southampton, who attacked with renewed vigour, with Gaston Ramirez running at the Reading goal before scuffing wide from distance.
The Uruguayan came closer moments later with a header as Saints pushed for an opener that came in the 34th minute.
The goal owed as much to poor defending as fine attacking play, with an impressive team move ending with Rodriguez playing a one-two with Rickie Lambert before bundling home through Adam Federici's legs.
The Australian goalkeeper, returning after a knee injury, should have done better and was beaten by Southampton's £6million striker again, only for his fierce strike to rattle the crossbar.
Rodriguez has shone since Pochettino's arrival on the south coast and his that confidence was epitomised two minutes from half-time, showing incredible pace to burst past the Reading backline.
Federici did well to save the striker's right-footed shot when clear on goal, with Ramirez putting the follow up just wide.
It was a bad end to a half in which Reading had started so well, with Adkins replacing Hope Akpan with Mikele Leigertwood after the break.
Much like the opening period, the hosts were again quicker to settle but failed to turn possession into clear-cut opportunities.
That allowed Saints to return to the attack and, after Federici easily dealt with a tame Steven Davis effort, a fine driven Rodriguez cross just evaded Lambert at the far post.
Le Fondre struck wide as Reading searched for an equaliser, although Saints were still looking dangerous themselves.
After striking an audacious 25-yard effort wide, Rodriguez put through substitute Lallana to slot home at Federici's near post to send the 2,216 visiting fans into raptures.
It was no less than Pochettino's side deserved but Reading thought they had pulled one back through Le Fondre. Boruc spilled the former Rotherham forward's header but was adjudged to have stopped the ball crossing the line, much to the home fans' annoyance.
There was to be no late drama, although Saints substitute Guly do Prado should have found the target in stoppage time.