The injury curse has struck again at the start of this season for Sunderland, as Moyes revealed in friday's pre-match press conference that first choice goalkeeper Vito Mannone will be out for three months with elbow ligament damage he picked up in training on tuesday.
Local born 22-year-old Jordan Pickford deputised in the 1-0 League Cup win over Shrewsbury Town on wedenesday night and unless the club makes a serious move in the transfer window for a keeper, then Pickford will be the number one untill the end of the calender year and obviously play in this game.
This area of the pitch was the only one unchanged from the Middlesbrough game going into the mid-week cup match. There could well be a couple of changes to the back four on the south coast, though. Atletico Madrid right back Javier Manquillo arrived on a season-long loan in the week and could take the place of Donald Love after the criticism the youngster has received during the first two games of the season.
At full-back, Moyes has no alternative option to Patrick Van Aanholt even after a mixed start to the campaign for the Dutchman. It's clear to see how important he is to the team in an attacking sense, but he's arguably been at fault for three of the four goals the team have conceded this season and remains suspect defensively.
Moving onto the centre-backs and one of them is an obvious pick in the form of Papi Djilobodji who has settled in quickly after his move from Chelsea, with some assured performances in the last last couple of games.
As for his starting partner, it could well change for the third time in six days after John O'Shea started in the Wear-Tees derby, but was then substituted due to a hamstring inury. Jack Rodwell filled in for the cup match and played well, albeit against lower quality opposition and perhaps is favourite to start in this one.
However, Moyes revealed there is a chance of Lamine Kone being back in the team after he took part in light training on Thursday and is set to take part in a full session on Friday before being assessed ahead of the game at St. Mary's Stadium.
So far Moyes has opted to go with a 4-2-3-1 formation in the league, but with the defensive and midfield injury problems he has had to play midfielders as makeshift defenders and, therefore, this takes away his options in terms of holding midfielders. If Kone does return in defence then Moyes shouldn't have to do this again.
Assuming Kone does start the match then Rodwell should return to the midfield and play in a holding role - most likely alongside Paddy McNair, who has struggled to get going in a Sunderland shirt but with no other naturals in this position fit he should keep his place.
As for the options further forward, Lynden Gooch, Wahbi Khazri and match winner Januzaj all started in the cup match and they'd be favourites to start again in an advanced midfield trio behind lone striker Jermain Defoe.
However, like Kone, Moyes said forward Fabio Borini will be asessed perhaps could force his way into the team instead of Khazri, who it seems is not fancied by the manager. new signing Steven Pienaar is another wide option and could provide Moyes with a different system.
Another position in the team, which is somewhat set by the lack of depth in the squad, but more so by the quality of the man who fills it, Jermain Defoe. Moyes perhaps wisely gave Defoe the night off completely against Shrewsbury with youngster Joel Asoro getting his first senior team start and applying himself well, but he understands Defoe is the main man on Wearside.
Predicted XI (4-2-3-1)
Pickford; Manquillo, Kone, Djilibodji, Van Aanholt; Rodwell, McNair; Januzaj, Gooch, Khazri; Defoe.