It's a big blow to West Coast who is already missing its two half-back flankers in Shannon Hurn (knee, six weeks) and Beau Waters (shoulder, season).
Sharrod Wellingham (soreness) was a late withdrawal before the match.
But the Eagles covered the absences well despite a scare from a gutsy St Kilda outfit that led by 13 points midway through the third term.
West Coast was forced to claw its way back, kicking seven of the last eight goals in a night ruckman Dean Cox equalled Glen Jakovich's club games record of 276.
Cox kicked the last goal of the match but not before St Kilda made his side earn the win.
The Saints midfield, led by Leigh Montagna, Luke Dunstan, and Farren Ray, dominated the clearances and the contested possession count but let themselves down with their conversion in front of goal.
"All credit to St Kilda," Simpson said. "They did come over with a hunt mentality.
"We're quite proud of the boys to guts it out.
"We were in a bit of strife there. We had personnel who were down but also the way we were playing wasn't the way we've been playing the last few weeks."
St Kilda coach Alan Richardson was pleased with the Saints effort but felt turnovers cost them dearly.
"We thought we were really strong in terms of effort and contest - putting the Eagles under pressure," Richardson said.
"The Eagles scored 8.8 on the back of turning our footy over.
"We were well and truly solid defensively but didn't maximise when we turned the footy over."
The Eagles made a fast start with Luke Shuey kicking the first goal within a minute of the opening bounce.
The Saints then silenced the home crowd with a dominant 15-minute period.
The visitors controlled the clearances and out-pointed the Eagles around the contest but could not convert their chances in front of goal. They kicked just 1.5 for the term and two late goals to the Eagles' tall timber of Josh Kennedy and Callum Sinclair saw the home side lead by nine points at quarter-time.
Xavier Ellis kicked the first goal of the second quarter as the Eagles threatened to dash clear but the Saints dug in and their skipper Nick Riewoldt took control. He imposed himself on the contest with typical gut-busting running. Riewoldt kicked consecutive goals from marks before Montagna added two more to give the Saints an eight-point lead at half-time.
The third term was an arm-wrestle but again the Saints had their opportunities. Eli Templeton converted a tight set-shot but missed an easier chance on the run that would have extended the lead to 18.
The Eagles seized on the let-off kicking three consecutive goals to lead by six points at the final change.
The home side ran away with it in the end kicking four goals to one in the final term, with Cox ending his milestone match on a high with the final goal.
Cox had 34 hit-outs, 15 possessions and a goal in another standout performance, while Matt Priddis ( 28 touches, one goal) and Jack Darling (17 possessions, six tackles) were also impressive.
Dean Cox celebrates the final goal of the contest in his record-equalling game. Picture: AFL Media
WEST COAST 3.2 5.4 8.8 12.11 (83)
ST KILDA 1.5 6.6 7.8 8.10 (58)
GOALS
West Coast: Ellis 2, Cripps 2, Kennedy 2, Darling, Shuey, Sinclair, Cox, Priddis, Brown
St Kilda: Riewoldt 2, Montagna 2, Dunstan 2, Maister, Templeton
BEST
West Coast: Priddis, Darling, Cox, Gaff, Ellis, Glass, Sheppard, Bennell
St Kilda: Montagna, Riewoldt, Dunstan, Hayes, Ray, Armitage
INJURIES
West Coast: Wellingham (groin) replaced in selected side by Schofield, LeCras (arm)
St Kilda: Gilbert (foot)
SUBSTITUTES
West Coast: Mark LeCras (arm) replaced by Will Schofield in first quarter
St Kilda: Sam Gilbert (foot) by Shane Savage in the first quarter
Gemma Bastiani delves into stars of the 2024 Telstra AFLW Draft
10:57
The most spectacular marks of 2024
Relive the best marks of the 2024 Toyota AFL Premiership season
01:21
Why McDonald could become AFLW's best key forward
Gemma Bastiani delves into stars of the 2024 Telstra AFLW Draft
00:15
Opening Round QLD | March 6-9
Be part of AFL Opening Round to kick-off the 2025 Toyota AFL Premiership Season in QLD. March 6-9. Brisbane Lions host Geelong at the GABBA and Gold Coast SUNS take on Essendon at People First Stadium.