With Sam, 24, returning from suspension, it will be the first opportunity the English-born quartet of siblings have had to play in the same side.
Sam and Luke, 26, will both start against Wests Tigers at Allianz Stadium on Friday, with twins, Tom and George both 21, coming off the bench.
"To see them all work extremely hard, it's (playing together) obviously something as a group they've been really keen to achieve," Maguire said on Wednesday.
"And it's through merit, they thoroughly deserve their positions. Everyone is looking forward to a game like this with four brothers."
All four brothers weigh over 110 kilos and Maguire could not remember fielding such a large collection of forwards.
The Rabbitohs also have considerable size in the backs, with fullback Greg Inglis and five-eighth John Sutton both listed at 105kg.
Asked if a side could ever get too big, Maguire said: "I guess you look at the side and the way you play.
"We adapt our game around the people we have in the team.
"We are just utilising our big men and Sutto (Sutton) and (half-back) Adam (Reynolds) and little Luke Keary coming in now, they are playing off the back of that and it's giving opportunities for our edges."
While wins in their last two games will secure Souths the minor premiership, Maguire said he was only thinking about the Tigers' fixture.