It will be Chelsea's first visit to the 80,000-seat arena since their heartbreaking loss in the 2008 final against Manchester United in a penalty shootout when captain John Terry slipped on wet grass and missed the decisive spot-kick.
The London club and their Russian billionaire owner Roman Abramovich will hope to avoid another slip-up this time, with the match being played on an artificial turf.
For Spartak, holders of the unenviable record of 22 successive Champions League games without a win that stretched for more than five years between 2001 and 2006, Tuesday's match will be the stiffest test yet of their European ambitions.
The Russians, who like Chelsea have a 100 percent record in the group after beating French champions Olympique Marseille and Slovakia's Zilina in their first two games, are well aware that another win would almost certainly secure them a place in the knockout round for the first time since the 1995-96 season.
"We had a great start, probably better than some of our fans had expected," Spartak coach Valery Karpin told local media.
"But we all know that beating Chelsea would be a totally different proposition from what we had before. So we're not getting carried away by any means."
Despite stumbling slightly in their march to their second consecutive Premier League title, Chelsea still have a two-point lead at the top after eight matches following their superb start to the season when they won five games on the trot.
INJURY PROBLEMS
Both teams have had a spate of injuries in recent weeks.
The English champions are still without key midfielder Frank Lampard but top marksman Didier Drogba could be available after serving a two-game European ban from last season.
Drogba, who has scored six times this season, is one of several faces manager Carlo Ancelotti hopes to welcome back on Tuesday after the Ivory Coast striker missed Saturday's 0-0 draw with Aston Villa with a fever.
Ancelotti can also count on fellow strikers Salomon Kalou and Daniel Sturridge and defender Alex after he recovered from a thigh injury but his Brazilian compatriot and namesake in the Spartak midfield has been ruled out with the same problem.
Aside from missing their playmaker, who was injured in Friday's 3-0 league win over Alania Vladikavkaz shortly after scoring a goal, Spartak are fretting over the fitness of leading striker Welliton and Ireland winger Aiden McGeady.
Chelsea's Russian left back Yuri Zhirkov is likely to face a heated reception from Spartak fans if he plays after being with their bitter Moscow rivals CSKA for five years before joining the London club in 2009.
Team (probable):
Spartak Moscow: 81-Andriy Dykan; 15-Sergei Parshyvlyuk, 19-Nicolas Pareja, 17-Marek Suchy, 16-Yevgeny Makeyev; 2-Christian Maidana, 64-Aiden McGeady, 5-Alexander Sheshukov, 99-Dmitry Kombarov; 9-Ari, 11-Welliton.
Chelsea: 1-Petr Cech; 2-Branislav Ivanovic, 33-Alex, 26-John Terry
