| Date | Opponent | Venue | Result | Attendance | Scorers |
|---|---|---|---|---|---|
| 13 August 2005 | Tottenham Hotspur | H | 0-2 | 20,215 | |
| 20 August 2005 | West Bromwich Albion | A | 1-2 | 24,404 | Robert |
| 23 August 2005 | Aston Villa | H | 1-1 | 19,778 | LuaLua |
| 27 August 2005 | Manchester City | A | 1-2 | 41,022 | Viafara |
| 10 September 2005 | Everton | A | 1-0 | 36,831 | Ferguson (og) |
| 17 September 2005 | Birmingham City | H | 1-1 | 19,319 | LuaLua |
| 20 September 2005 | Gillingham | A | 2-3 (AET) | 4,903 | O’Neil, Taylor |
| 24 September 2005 | Bolton Wanderers | A | 0-1 | 23,134 | |
| 1 October 2005 | Newcastle United | H | 0-0 | 20,220 | |
| 15 October 2005 | Middlesbrough | A | 1-1 | 26,551 | O’Neil |
| 22 October 2005 | Charlton Athletic | H | 1-2 | 19,030 | Silva |
| 29 October 2005 | Sunderland | A | 4-1 | 34,926 | Vukic, Taylor (2), Silva |
| 5 November 2005 | Wigan Athletic | H | 0-2 | 19,102 | |
| 19 November 2005 | Liverpool | A | 0-3 | 44,394 | |
| 26 November 2005 | Chelsea | H | 0-2 | 20,182 | |
| 3 December 2005 | Manchester United | A | 0-3 | 67,684 | |
| 12 December 2005 | Tottenham Hotspur | A | 1-3 | 36,141 | LuaLua |
| 17 December 2005 | West Bromwich Albion | H | 1-0 | 20,052 | Todorov |
| 26 December 2005 | West Ham United | H | 1-1 | 20,168 | O’Neil |
| 28 December 2005 | Arsenal | A | 0-4 | 38,223 | |
| 31 December 2005 | Fulham | H | 1-0 | 19,101 | O’Neil |
| 2 January 2006 | Blackburn Rovers | A | 1-2 | 19,521 | Taylor |
| 7 January 2006 | Ipswich Town | A | 1-0 | 15,593 | Silva |
| 14 January 2006 | Everton | H | 0-1 | 20,094 | |
| 21 January 2006 | Birmingham City | A | 0-5 | 29,138 | |
| 29 January 2006 | Liverpool | H | 1-2 | 17,247 | Davis |
| 1 February 2006 | Bolton Wanderers | H | 1-1 | 19,128 | Karadas |
| 4 February 2006 | Newcastle United | A | 0-2 | 51,627 | |
| 11 February 2006 | Manchester United | H | 1-3 | 20,206 | Taylor |
| 25 February 2006 | Chelsea | A | 0-2 | 42,254 | |
| 4 March 2006 | Aston Villa | A | 0-1 | 30,194 | |
| 11 March 2006 | Manchester City | H | 2-1 | 19,556 | Mendes (2) |
| 18 March 2006 | West Ham United | A | 4-2 | 34,837 | LuaLua, Davis, Mendes, Todorov |
| 1 April 2006 | Fulham | A | 3-1 | 22,322 | O’Neil (2) LuaLua |
| 8 April 2006 | Blackburn Rovers | H | 2-2 | 20,048 | LuaLua, Todorov |
| 12 April 2006 | Arsenal | H | 1-1 | 20,230 | LuaLua |
| 15 April 2006 | Middlesbrough | H | 1-0 | 20,204 | O’Neil |
| 17 April 2006 | Charlton Athletic | A | 1-2 | 25,419 | D’Alessandro |
| 22 April 2006 | Sunderland | H | 2-1 | 20,078 | Todorov, Taylor (pen) |
| 29 April 2006 | Wigan Athletic | A | 2-1 | 21,126 | Mwaruwari, Taylor (pen) |
| 7 May 2006 | Liverpool | H | 1-3 | 20,240 | Koroman |
