Jewell, though, insisted it was the right decision to rotate the squad as his priority is promotion to the Premiership.
But he did have a blast at the players who turned out at Pride Park, describing the display as "awful from start to finish."
Latics led until 19 minutes from time through Alan Mahon's first-half strike before goals from Inigo Idiakez and Junior turned the tie in the Rams' favour.
Jewell said: "It wasn't a gamble to change the team because I'm thinking long term about the league and about the amount of games we've had recently.
"Of course it's disappointing to lose but the FA Cup is not as important as the league to us.
"I'm told we've not made it to the fourth round for 18 years but we haven't been second in the table either.
"The league is our main objective and that is what I had to consider when deciding to rest players."
Top scorer Nathan Ellington was left out of the squad because of an ongoing hamstring injury, while Lee McCulloch also stayed at home after becoming a father on Friday.
Jimmy Bullard, Nicky Eaden and Leighton Baines were all named among the substitutes following the recent busy schedule.
Those who took their places didn't particularly impress Jewell, and the big guns will return for this weekend's visit to Rotherham where new signing Andreas Johansson could also be given a debut.
He said: "I thought we were awful from start to finish to be perfectly honest.
"It showed that if you get away from the work ethic that we pride ourselves on, you won't get anything.
"You can't turn that on and off like a tap and it's something I made perfectly clear to them afterwards.
"We changed the team a lot but I expected a lot more from the lads we did play.
"It's disappointing to have lost in that manner and I thought we under-
performed.
"Derby had a bit of pressure early on but I wouldn't say they had too many chances to take the lead.
"When we actually started getting the ball down and passing it, their keeper had to make three world class saves from Jason Roberts, Mike Flynn and the one from David Graham right at the end.
"But for me, we didn't show enough bottle, enough desire and I'm disappointed with a lot of players.
"The work-rate isn't a bonus, it's something that has to be taken as read.
"A lot of players had opportunities against Derby after not being in the side for a while, and they haven't taken advantage.
"But even some of the lads who have been in the team disappointed me.
Making the changes might have transmitted itself to the players, but there was a game of football to be won, we have people coming in to watch and people travelled from Wigan."
To cap a disappointing weekend, central defenders Matt Jackson and Ian Breckin both picked up injuries.
Jackson needed stitches to close a cut on the webbing of his hand while Breckin broke his nose after coming on as substitute for the skipper.
But it is expected that both will be fit to face Rotherham.
Jewell said: "Jacko hurt his hand and has had to have it stitched together. He did the same thing at Oldham a couple of years ago.
"Breckin got a broken nose as well, and the last thing you want is two of your centre-halves getting injured.
"It's something we could have done without but I don't think the injuries are too major and hopefully they'll be okay."