The Magpies were beaten by Sky Bet League One opposition for the second season running as two goals from Josh Windass gave the Owls a memorable third-round win at Hillsborough after Bruno Guimaraes had pulled one back.
Howe made eight changes to his team and was planning to give the French winger a start as he builds up his fitness following a hamstring injury until he was ruled out with illness.
Howe said: “Absolutely, it was a huge disappointment that he missed out. We thought it would be an ideal match for him to build his fitness and match time after his hamstring injury.
“But sometimes these things are just meant to be, it happened and hopefully he will be back soon.
“We hope just to get him back to full fitness because he is a game changer, a matchwinner and I think you could see, with him in the team, that result is potentially different.
“All we can do is get him back to his best as quickly as possible.”
Newcastle had more than enough chances to at least earn a replay against their hosts, with Alexander Isak, making his first appearance since mid-September, seeing two efforts saved by Owls goalkeeper Cameron Dawson.
That became a bit of a theme as Dawson also saved brilliantly from Elliot Anderson and Jacob Murphy in the second half as Wednesday produced their best result since beating Arsenal in the League Cup in 2015.
Dawson told the club’s official website: “It reminded me of the Arsenal one a few years ago, there was a full away following from Newcastle and a proper cup tie.
“The lads were resolute and dug in, scored two good goals and just managed to get over the line at the end with some bodies on the line. So we got the job done.
“It is always nice to save one early, against a top Premier League outfit your goalie is probably going to have to make some saves so it was nice tonight to be able to make a few.
“I’d have liked a clean sheet but that is being a bit greedy. We’ll take the win and see who we get in the next round.”