Arsenal's star midfielders are sidelined with shoulder and thigh concerns, respectively, with the Gunners looking to continue their fine form into the new year.
Having been briefly replaced at the top of the table by Manchester City on Saturday, Arsene Wenger's men returned to the summit 24 hours later courtesy of a battling 1-0 win at in-form Newcastle United.
Arsenal will be confident of picking up three points against Cardiff, which has mustered just one win in nine games and sits 16th in the table, two points above the relegation zone.
The Welsh outfit is also coming to terms with last week's sacking of manager Malky Mackay, which followed a prolonged public spat with club owner Vincent Tan.
David Kerslake is set to be in caretaker charge once again at the Emirates Stadium on Wednesday.
Kerslake oversaw Saturday's 2-2 home draw with Sunderland, which saw the league's bottom club come from two goals down to snatch a point, and is hopeful Cardiff can build on its display against Arsenal in the reverse fixture in November.
Although last season's Championship winner was beaten 3-0 that day, with former Cardiff midfielder Aaron Ramsey scoring twice, Arsenal only made the game safe with two goals in the final four minutes.
"We held our own against them," said Kerslake. "We know they are one of the finest sides in Europe. We had a good go at them here, so we go there in good spirits."
Cardiff's last victory over Arsenal came in Feb. 1961, although the two sides have only met 12 times since.
German playmaker Mesut Ozil is likely to be unavailable for Wenger's men, having missed the win over Newcastle with a shoulder injury.
Ramsey, one of the standout players in the Premier League this season, remains sidelined by a thigh problem, while Cardiff's Craig Bellamy is still battling a knee complaint.
Arsenal is unbeaten in eight league home games since losing to Aston Villa on the opening day of the season, but has been held to draws by Everton and Chelsea in the team's last two matches at the Emirates Stadium.
Cardiff's only away win to date came at Fulham on Sept. 28.