The Wimbledon champion has been relatively untroubled in his opening two matches on his return to Roland Garros, although he did lose a set to Andrey Golubev in round one.
Against Australian Marinko Matosevic, Murray was impressive, dropping just seven games in three sets, but Kohlschreiber represents a significant step up.
The German is the 28th seed and on a six-match winning run after clinching the title in Dusseldorf last week.
Of Kohlschreiber's five ATP Tour singles titles, three have come on clay, and he has made three more finals on the surface.
That is a significantly better record than Murray, who is still looking for his first clay-court final, although he does not play in the smaller events where Kohlschreiber has had success.
The Scot said: "It's a very tough match for me. I played him once before on clay and I think I got three games or something.
"He obviously won the tournament last week. He's not dropped a set here, I don't think. So, yeah, he will be very tough, he's a very good player."
That previous meeting came in Monte Carlo four years ago when Kohlschreiber won 6-2 6-1 in little more than an hour and Murray was jeered off court.
At the time he labelled it one of the worst performances of his career, saying: "I was just rubbish. I played a rubbish match."
He appears to have blanked the worst details from his mind, and neither man will feel that match has any bearing at all on this contest.
Murray said: "I remember not playing particularly well. I was very disappointed after the match.
"Over the years I have had a few matches like that in Monte Carlo where I've lost fairly comfortably. I lost to Stan (Wawrinka) last year very quickly, as well.
"At the beginning of the clay-court season I have had some tough matches over the years, so I don't remember a whole lot about it in terms of exactly what happened during the match. It just wasn't a pleasant memory for me."
Murray and Kohlschreiber are both in Paris without a main coach.
While the speculation continues about who Murray will pick to replace Ivan Lendl, Kohlschreiber's long-term coach Markus Wislsperger is back in Germany, with the pair set to decide after the tournament whether to continue working together.
The 30-year-old feels a lot on Saturday will depend on which Murray turns up - the one who pushed Rafael Nadal all the way in Rome or the one who folded so meekly to Santiago Giraldo a week earlier in Madrid.
Kohlschreiber said: "It all depends on his level of play, I would say. If the big guys are confident and they win many matches, they're going to be tough to beat.
"Obviously I'm also on a very nice run at the moment, so it's the best chance at the moment to play against the big guys.
"For sure he's the favourite in this match, but I'm going to try everything and fight from the first to last point. I'm going to enjoy this match.
"If he's fit and mentally strong, he's unbelievably tough to play. He's a very solid player. He's a big fighter. You're going to work very hard for the points.
"Obviously over the last years he's in the top four, top five. Okay last year he had a much tougher year with the injury, but I think he's coming back stronger and stronger."
Kohlschreiber, who cited clay as the surface on which he would most like to play Murray, is no stranger to big matches at grand slams and is the last player to beat Novak Djokovic before the quarter-finals of a major.
That came here in 2009, while he won sets against both Djokovic and Nadal in grand slams last year.
He said: "I have a lot of confidence at the moment. And winning a title is always very special. It came at a great time, let's put it this way. I'm just enjoying at the moment the good run."