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Top scorer Nathan Ellington and winger Lee McCulloch were left out of the starting line-up at the Britannia Stadium and named as substitutes.
And skipper Jason de Vos together with influential midfielder Tony Dinning didn't make the travelling squad at all in order to protect injuries they have been carrying.
The choice of selection backfired with Latics slumping to a 3-0 defeat but Jewell had no regrets about it.
Jewell said: "I made the changes as we had one or two knocks and I didn't want to take any chances.
"Jason has a problem with his foot at the moment while Tony has a slight back injury.
"Lee has just come back from a long time out injured and I felt justified in resting him.
"We are disappointed to be out of the FA Cup but it isn't as important to us this season as the league is."
Ellington and McCulloch both came on as substitutes at the start of the second half but couldn't spark a revival.
Latics were 2-0 down by then and went on to concede a third midway through the second-half as their 12-match unbeaten away run came to an end.
It was the first time Jewell had seen his side ship three goals in a game since the 3-2 defeat against Colchester 14 months ago.
The boss, who collected his Nationwide Manager of the Month award for December at Wrightington today, felt the 3-0 scoreline was harsh on his players.
Jewell added: "There certainly weren't three goals in it but we weren't at our best.
"We missed key players in key areas and that showed.
"This season we have been a difficult side to play against, but we were a bit too easy to play against at Stoke.
"Saying that, we had three or three good chances to score at 2-0, but then Stoke went down the other end and scored with their first shot of the second half.
"We had as much possession as Stoke did, but they were more clinical than we were.
"Looking at the positives, we haven't lost any league points and this was only the fifth game we have lost all season.
"Apart from Port Vale in August, every time we have had a defeat we have bounced straight back.
"We are all disappointed at the moment but this is done now and we have to look forward to going to Bristol City on Friday."
Jewell wasn't exactly overjoyed with the performance of the officials, confronting referee Alan Butler and his assistants at the end of the first-half.
But afterwards all he said was: "To be fair to him, I think the linesman actually got the jewellery check right.
Article from the Wigan Evening Post.