| | "Date","Opponent","Venue","Result","Attendance","Scorers" |
| | "13 August 2005","Charlton Athletic","Stadium of Light","1–3","34,446","Gray" |
| | "20 August 2005","Liverpool","Anfield","0–1","44,913","" |
| | "23 August 2005","Manchester City","Stadium of Light","1–2","33,357","Le Tallec" |
| | "27 August 2005","Wigan Athletic","JJB Stadium","0–1","17,223","" |
| | "10 September 2005","Chelsea","Stamford Bridge","0–2","41,969","" |
| | "17 September 2005","West Bromwich Albion","Stadium of Light","1–1","31,657","Breen" |
| | "25 September 2005","Middlesbrough","Riverside Stadium","2–0","29,583","Miller, Arca" |
| | "1 October 2005","West Ham United","Stadium of Light","1–1","31,212","Miller" |
| | "15 October 2005","Manchester United","Stadium of Light","1–3","39,085","Elliott" |
| | "23 October 2005","Newcastle United","St James' Park","2–3","52,302","Lawrence, Elliott" |
| | "29 October 2005","Portsmouth","Stadium of Light","1–4","34,926","Whitehead (pen)" |
| | "5 November 2005","Arsenal","Highbury","1–3","38,210","Stubbs" |
| | "19 November 2005","Aston Villa","Stadium of Light","1–3","39,707","Whitehead (pen)" |
| | "26 November 2005","Birmingham City","Stadium of Light","0–1","32,442","" |
| | "30 November 2005","Liverpool","Stadium of Light","0–2","32,697","" |
| | "3 December 2005","Tottenham Hotspur","White Hart Lane","2–3","36,244","Whitehead, Le Tallec" |
| | "10 December 2005","Charlton Athletic","The Valley","0–2","26,065","" |
| | "26 December 2005","Bolton Wanderers","Stadium of Light","0–0","32,232","" |
| | "31 December 2005","Everton","Stadium of Light","0–1","30,567","" |
| | "2 January 2006","Fulham","Craven Cottage","1–2","19,372","Lawrence" |
| | "15 January 2006","Chelsea","Stadium of Light","1–2","32,420","Lawrence" |
| | "21 January 2006","West Bromwich Albion","The Hawthorns","1–0","26,464","Watson (own goal)" |
| | "31 January 2006","Middlesbrough","Stadium of Light","0–3","31,675","" |
| | "4 February 2006","West Ham United","Boleyn Ground","0–2","34,745","" |
| | "12 February 2006","Tottenham Hotspur","Stadium of Light","1–1","34,700","Murphy" |
| | "15 February 2006","Blackburn Rovers","Ewood Park","0–2","18,220","" |
| | "25 February 2006","Birmingham City","St. Andrew's","0–1","29,257","" |
| | "3 March 2006","Manchester City","City of Manchester Stadium","1–2","42,200","Kyle" |
| | "11 March 2006","Wigan Athletic","Stadium of Light","0–1","31,194","" |
| | "18 March 2006","Bolton Wanderers","Reebok Stadium","0–2","23,568","" |
| | "25 March 2006","Blackburn Rovers","Stadium of Light","0–1","29,593","" |
| | "1 April 2006","Everton","Goodison Park","2–2","38,093","Stead, Delap" |
| | "14 April 2006","Manchester United","Old Trafford","0–0","72,519","" |
| | "17 April 2006","Newcastle United","Stadium of Light","1–4","40,032","Hoyte" |
| | "22 April 2006","Portsmouth","Fratton Park","1–2","20,078","Miller" |
| | "1 May 2006","Arsenal","Stadium of Light","0–3","44,003","" |
| | "4 May 2006","Fulham","Stadium of Light","2–1","28,226","Le Tallec, Brown" |
| | "7 May 2006","Aston Villa","Villa Park","1–2","33,820","D. Collins" |
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