Spartak are eight points clear of both city rivals CSKA and Zenit with eight matches to go.
Spartak, who won the last of their nine titles in 2001, are eight points clear of both city rivals CSKA and Zenit with eight matches to go.
But Zenit, who beat Spartak 4-2 in October, are hoping to do the double over the Muscovites to stay in the hunt following a disappointing 1-1 draw with Anzhi Makhachkala last time out.
Manager Mircea Lucescu was upset with Zenit's sub-par performance a week ago and expects his players to rediscover their best form in a clash against arch rivals.
"Some of our team leaders played too cautiously in the match against Anzhi due to the threat of missing the clash with Spartak through suspension," Lucescu told the Zenit website.
"We were just a pale shadow of our normal self, especially in the first half. But I'm confident that on Sunday we will see a completely different Zenit."
Spartak skipper Denis Glushakov said there would be no complacency within the squad, with matches still to play against both their title rivals ensuring the race is far from finished.
"For us each of the remaining games will be the match of the year," Glushakov said. "There are eight matches ahead and we must play for the win in every one.
"Of course the meetings with Zenit or CSKA are always important but a single match decides nothing. We should gear up for each of these eight games as if it's the biggest one."
On Saturday reigning champions CSKA will host a Rostov side that has kept a clean sheet in all five of their matches -- including four straight 0-0 draws -- since the league resumed following the winter break.
CSKA head coach Viktor Goncharenko said the results of this weekend's matches and his side's clash with Spartak on April 30 would likely determine this season's title winner.
"We try not to take into consideration our rivals' results as we know clearly that we need to play for the win in every game," he told CSKA's website.
"I think that the results of the games in the upcoming weekend will be crucial in terms of who wins the title. The outcome of our derby with Spartak will also have an impact."
Fixtures (all times GMT)
Amkar Perm v Ufa (0900), CSKA v Rostov (1130), Anzhi Makhachkala v Samara (1400), Rubin Kazan v Krasnodar (1630)
Orenburg v Terek Grozny (0930), Ural Yekaterinburg v Tomsk (1200), Arsenal Tula v Lokomotiv Moscow (1430), Spartak Moscow v Zenit St Petersburg (1700)