Third-placed Boro head into the game on the back of a 2-0 loss at Wolves in midweek, their first league defeat in nine matches and first on the road since August 16 when they lost out 1-0 at Leeds United.
Watford boast a seven-match unbeaten streak going into proceedings and do battle with hosts who are without suspended seven-goal top scorer Leadbitter.
Adam Clayton, recovered from a head injury, is set to replace Leadbitter, with head coach Karanka likely to make other changes having admitted that he got the make-up of his line-up at Molineux on Tuesday wrong.
The game will represent a test of Boro’s mettle without midfield talisman Leadbitter and Karanka is seeking a response.
He said: “It’s a good game to forget our last performance and it is a good test for us because Watford are a team that are above us and they are a very good team.
“Both of us are in a good position, but it is very early and we have to keep going in the same way.
“So if you play a team in a similar position to you, you have to try to beat him because it is more than three points.”
On being without Leadbitter, he added: “I am confident we can cope without him.
“He is very important for the team, but whichever player I put in the team on Saturday will do his job 100 per cent.
“I have a very good squad, the one I wanted three or four months ago. Grant is not going to play on Saturday, but there are other players that I trust.”
Luke Williams has joined League One strugglers Scunthorpe United on a month’s loan.