Arsenal hosts Manchester United in a major test for teams looking to challenge Manchester City for the title.
Both sides are hoping their first-choice striker will be fit to make a first start to the season, with Gabriel Jesus and United newcomer Rasmus Hojlund having recovered from injuries.
Liverpool hosts Aston Villa in another marquee matchup after rebuffing late interest from Saudi Arabia for Mohamed Salah. Crystal Palace welcomes Wolverhampton.
Portugal players João Cancelo and João Félix are on Barcelona’s squad for its visit to Osasuna after they joined the club just before the close of the summer transfer window on Friday.
Iñigo Martínez could also make his debut after the former Athletic Bilbao defender recovered from an injury that has kept him from playing since signing for Barcelona this summer.
Atletico Madrid hosts a Sevilla side in a nosedive after losing its first four of games in all competitions. Girona hosts Las Palmas aiming to keep up its surprisingly strong start of two wins and a draw. Athletic Bilbao is at Mallorca.
Inter Milan hosts Fiorentina looking to extend its perfect start. The Nerazzurri have won both of their initial matches by 2-0, with Lautaro Martinez scoring three of the four goals.
Fiorentina will be playing its fifth match of the season, having just qualified for the Conference League group phase by beating Rapid Vienna 2-0 on Thursday with a brace from Nicolas Gonzalez.
Juventus visits Empoli looking to rebound from an unimpressive 1-1 draw with Bologna. Also, it’s: Torino vs. Genoa and Lecce vs. Salernitana.
Italy captain Leonardo Bonucci could make his Bundesliga debut for Union Berlin against visiting Leipzig.
Bonucci joined Union on the last day of the transfer window and could play depending on the fitness of Danilho Doekhi, who broke his cheekbone while scoring in the 4-1 win over Darmstadt.
Union surprised most people by finishing fourth last season and has made a perfect start to the league again. Leipzig responded to its opening loss to Bayer Leverkusen by routing Stuttgart 5-1.
Union has won the last league meetings with Leipzig, all by 2-1 scorelines. The Köpenick-based team is unbeaten in a club-record 24 league games at home. Cologne is Eintracht Frankfurt’s first game since selling star forward Randall Kolo Muani to Paris Saint-Germain for a club-record 95 million euros ($102.5 million).
Defending champion Paris Saint-Germain travels to play struggling Lyon after a busy transfer window.
Winger Bradley Barcola has been included in coach Luis Enrique’s PSG squad, and Barcola is set to face a fierce reaction from the home fans after joining from Lyon this week in a deal worth 50 million euros ($54 million).
Forward Randal Kolo Muani, who joined PSG from Eintracht Frankfurt near the end of Friday’s transfer window for 95 million euros ($103 million), is nursing a sprained ankle.
Lyon has collected only one point so far. Elsewhere, unbeaten Lorient is at promoted Le Havre and Nice hosts Strasbourg.