The inspirational loose forward suffered a quadriceps strain against Tonga but hasn't recovered in time. Sam Burgess will skipper the side, a role he performed during the 2016 Four Nations, with Ben Currie starting and Jonny Lomax moving to the bench.
England ground their way to a patchy 29-10 win against Lebanon last week, with coach Wayne Bennett saying they "lost their way in the second half", and the Wigan Warriors captain wants more consistency at Perth Stadium.
Betts, a decorated former England captain who joined Wayne Bennett's coaching group last year, says O'Loughlin's consistency and big game temperament is an example for the other squad members to follow.