His father Keiron O'Loughlin also featured in the 1983–84 Challenge Cup Final for the Widnes side which achieved victory over Wigan.

[6] It was the Wigan-based amateur club Wigan St Patricks which gave Sean his first experience of competitive rugby league.

[10] In 2002, he also featured in two matches during the cross-code Middlesex Sevens tournament, playing as Scrum-half in a team composed of both Wigan and Orrell R.U.F.C.

[citation needed] O'Loughlin made his breakthrough into the Wigan first team under head coach Stuart Raper during 2002's Super League VII.

[12] Two weeks later, O'Loughlin scored his first tries for the club as a substitute against Warrington, and subsequently made six consecutive appearances from the bench.

He made his first starting appearance for Wigan during a 16–41 away victory against Warrington, when he was called upon to replace his injured brother-in-law, Andy Farrell.

After returning from the Middlesex Sevens event where he played Scrum-half, he made another starting appearance against Warrington, this time at Stand-off.

O'Loughlin played for the Wigan Warriors as a stand-off halfback in the 2003 Super League Grand Final which was lost to Bradford Bulls.

O'Loughlin played loose forward for most of 2004 with Andy Farrell moving to prop as cover for injuries.

[18] The poor start to the season left Wigan bottom of the Super League and led to the sacking of Ian Millward who was replaced by Brian Noble.

With O'Loughlin's contract expiring at the end of 2006 he was linked with a move to new Australian NRL side Gold Coast Titans for most of the season but in November 2006 he signed a new two deal with Wigan keeping him at the club until 2008.

O'Loughlin was forced to rule himself out of contention for the England training squad for the 2008 Rugby League World Cup through injury.

at Wembley Stadium,[23][24][25] and the 2013 Super League Grand Final 30–16 comeback victory over Warrington Wolves at Old Trafford.

The following year, following the international retirement of Kevin Sinfield, he was named as England captain ahead of the Four Nations tournament.

[43] O'Loughlin was appointed Officer of the Order of the British Empire (OBE) in the 2022 Birthday Honours for services to rugby league football.