New York Red Bulls will look to rein in MLS Eastern Conference leaders Montreal Impact when they face Philadelpia Union on Sunday.
The clash at PPL Park is set to be one of the stand-out fixtures of the weekend, as second take on third with both bidding to close the gap on the Impact.
Mike Petke's Red Bulls play for the first time since they lost 4-2 away at New England Revolution on June 12 and, after going without a win since May 29, they will be looking to get their title tilt back on track against the Union.
New York will once again rely heavily on top scorer Thierry Henry to get them the three points, with the Frenchman two ahead of Tim Cahill in the Red Bulls' goal standings on six strikes for the season.
However, their opponents will be seething after losing 3-1 to strugglers DC United, who notched up their only win of the season last time out.
Western Conference side FC Dallas top their table by just one point and they will be looking to gain some breathing space when they host Sporting Kansas City on Saturday.
They will also be boosted as Blas Perez is expected to return following international duty with Panama, while fellow striker Kenny Cooper, who was part of Manchester United's youth set-up, is also set for a comeback after a family emergency.
Schellas Hyndman's side have won four of their last five games but need another victory to keep their distance from Real Salt Lake and Portland Timbers - who are both just one point adrift - at the top of the table.
Both Salt Lake and Portland will teams play lower-placed opponents, with the former taking on Seattle Sounders on Saturday and the latter coming up against Colorado Rapids the next day.
Salt Lake finished second in their division last year before ending the season fifth overall, and have gone unbeaten at home for six games in a row this time around, meaning they are hot favourites for a win this weekend.
Portland Timbers will also have high hopes, as Colorado have failed to win a game since May 25.
The bottom of the table clashes will see Chivas USA and DC United attempt to move up their tables, with Chivas now eight points away from San Jose Earthquakes in the Western Conference.
The fledgling team will face LA Galaxy at the StubHub centre on Sunday, and they will be hoping the Galaxy continue their recent run of poor form, whcih has seen them go four games without a win, including a 5-0 loss to New England.
DC United will want to overcome the Earthquakes at home in the early kick-off on Saturday, but last year's overall winners are not in the best form themselves, and also need to move up the table.
The fixture is another big one for the Earthquakes, with interim coach Mark Watson's wanting to follow up their win in his first game oin charge with another three points.
The final two fixtures of the weekend will see Columbus Crew travel to Chicago Fire on Saturday. Colombus won 2-1 in the reverse fixture in January.
Houston Dynamo, who are fourth in the Eastern Conference, will come up against Toronto FC at the BBVA Compass Stadium on Saturday and will be looking to bounce back after losing 2-0 to Montreal on Wednesday.