The Premier League club sit three points behind their German opponents, who have yet to concede a goal in the Champions League this season
The Bundesliga side have made a superb start to their continental campaign, picking up a 3-0 home win over Steaua Bucharest on matchday one, and a 1-0 victory at Basel a fortnight later.
Chelsea, meanwhile, bounced back from a 2-1 opening-game defeat to the Swiss champions in the best possible way last time out - cruising to a 4-0 win in Romania.
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Schalke's domestic campaign has faltered, however, with Jens Keller's men picking up just four victories from their opening nine fixtures, although they head into this clash off the back of a 3-2 win at Eintracht Braunschweig on Saturday in which they were forced to come from behind twice.
The sides have met at this stage of the Champions League on one previous occasion - in 2007 - when Chelsea came away with a point from a goalless draw at the Veltins-Arena, having beaten the German side 2-0 at Stamford Bridge.
Both eventually qualified from that group, with Chelsea going on to lose the final on penalties to Manchester United.
Schalke will be looking to their top domestic goalscorer Adam Szalai to find his shooting boots in Europe, while Julian Draxler will aim to maintain his record of having scored in both matches in the group stages so far.
But the Bundesliga's fifth-placed side have a lengthy injury list to contend with, including striker Klaas-Jan Huntelaar, who is set to miss three to four months with a knee injury that will require surgery.
Midfielder Marco Hoger was also forced off in the weekend win with a torn cruciate ligament and is out for the long-term.
For Chelsea, Ashley Cole is a fitness concern after missing England's final two World Cup qualifiers and his club's win at the weekend with a rib injury, while Andre Schurrle was also absent for the Cardiff match due to a muscle problem in his leg.
Victory by one goal would be enough to send Chelsea above Schalke in the group.