After last week's win over Blackpool, Nigel Adkins made three changes to his starting line-up. Jake Cooper came in for the suspended Michael Hector, while Nick Blackman and Jake Taylor, perhaps surprisingly, came in for Simon Cox, and last week's man of the match, Jamie Mackie.
The Royals started promisingly with Glenn Murray heading against the bar from a corner.
Unfortunately though, Blackburn opened the scoring on 17 minutes. The lively Ben Marshall put a cross in and Rudy Gestede beat Jake Cooper to direct a powerful header past Adam Federici.
Despite the setback, Reading put in a lively first half performance, coming close through Taylor and then Oliver Norwood.
Just as it looked like the Royals decent opening 45 minutes would go unrewarded, a promising move led to Jordan Obita putting over a delicious low cross which Glenn Murray tapped in at the far post.
An even game was changed on the 55th minute when Marshall struck a beautiful free kick from distance which gave Federici no chance.
Nigel Adkins responded to the set back by bringing on Cox and Murray, for Robson-Kanu and Taylor.
But the changes made little difference as Blackburn extended their lead when the game's outstanding player Marshall, once again got the better of Chris Gunter, to put a dangerous cross over which Jordan Rhodes headed against the post, and Gestede fired home the rebound.
The defeat at Ewood Park leaves Reading in 15th place. Nigel Adkins now faces a massive week with two home games against Rotherham and Charlton.
We'll have a full report later, and player ratings tomorrow.