Manchester United will be without Lisandro Martinez and Kobbie Mainoo when they travel to the Emirates Stadium to face Arsenal tomorrow evening. Both started Sunday's 4-0 thrashing of Everton at Old Trafford but were skating on thin ice, having received four yellow cards previously in the Premier League this season.
Martinez and Mainoo went unscathed in the first half, but both were booked for fouls during three minutes of madness shortly after the interval.
And United's former chief scout, Mick Brown, has emphasised how devastating it is for Ruben Amorim to lose the duo for the toughest test of his short reign so far.
"Losing those two is a huge blow for them," Brown told Football Insider.
"Going away to Arsenal is going to be difficult at the best of times, so they could've done with two key players being available and in the team.
"Mainoo has been out injured, and they were selective about easing him back in.
He's an important player and a real gem, but just after getting him back to a good level of fitness, all of a sudden, he's missing again.
"Martinez looks like being the answer to the issues they've had at left-centre back, but he's out too.
"So Amorim is going to face a bit of an issue about how he's going to replace them.
"Does he go like-for-like, or does he change things slightly? He's got options in both positions, but it'll be difficult to maintain the level of quality with different players."
Amorim has stayed true to his 3-4-3 system in his opening three games - a 1-1 draw at Ipswich Town before 3-2 and 4-0 wins against Bodo/Glimt and Everton.
Although he has made minor in-game tweaks to turn the tides in his side's favour, the Portuguese tactician has ensured the principles have remained the same.
Harry Maguire returned from injury to earn his first minutes under the new boss at the weekend, while Luke Shaw made his third successive substitute cameo.
The latter could be in line for his first United start since February against Arsenal in Martinez's absence.
Meanwhile, Manuel Ugarte is waiting in the wings to replace Mainoo after his stellar showing in the Europa League victory over Glimt.
Mason Mount is another option to return to the front three, pushing Bruno Fernandes into the midfield two as in the match above.
How Amorim sets up in his first game in which United aren't expected to win is unsurprisingly causing intrigue en masse.