Holders Atletico Madrid kick off the defence of their UEFA Europa League title with a tricky away tie to Israeli club Hapoel Tel-Aviv on Thursday.
English Premier League trio Liverpool, Newcastle and Tottenham, as well as Italian heavyweights Inter Milan against Rubin Kazan, are all also in action and will be seeking to offer up better performances than their respective league representatives last time around.
Atletico Madrid, 3-0 victors over La Liga rivals Athletic Bilbao in last season's final, demolished Chelsea 4-1 in the UEFA Super Cup and will be looking to extend their European winning streak to 14 matches in the Group B clash.
Atletico right wing back Juanfran said: "We've made a very good start to the season, with good victories in the La Liga and in the Super Cup.
"We mustn't drop our guard, but follow on this path and try to be as strong and focused through until the end of the season.
"It's the goal of the team and the coach, that we're up all season long and that Atletico Madrid is where it needs to be in the year ahead."
Juanfran added: "We're in the Europa League and we must kick it off thinking that we want to get to the final. We must not think beyond each game. We've done very well not thinking beyond this week, with games against Hapoel and Valladolid, two matches we have to win.
New-look Reds aim high
Liverpool will be bidding to put up a better showing than the two Manchester clubs and Stoke, who all failed to shine in last year's competition.
Manager Brendan Rodgers is set to hand a debut to teenage striker Samed Yesil for the Group A match against Young Boys Berne.
But Rodgers will rest several senior stars for the Young Boys tie ahead of Manchester United's visit to Anfield on Sunday and that opens the way for Yesil to feature against the Swiss side.
"Yesil will certainly be fast-tracked," Rodgers said of the 18-year-old born to a Turkish family in Dusseldorf. "He will be involved in the Europa League game.
"I watched him play (for Germany) against England Under-19s during the international break and he scored two terrific goals and set up another."
Newcastle travel to Madeira to play Maritimo in Group D while Tottenham host Lazio in Group J.
After clinching a first Premier League victory of the season, 3-1 over Reading, last Sunday, Spurs manager Andre Villas-Boas turned his thoughts to the Europa League, saying: "We want to do something special in this competition.
Lazio have made a 100 per cent winning start in Serie A after three games and travel to London on the back of a 3-1 win at Chievo on Sunday.
"This competition is very important," said Villas-Boas, who insisted he will be fielding a 'strong team'.
"It's a tough competition, you have to play 15 games before you reach the final, so it's hard and strenuous and the best teams out of the Champions League are playing.
"It gives access to the European Super Cup and, for me, I always thought it was a prestigious competition and it should be promoted like that because after the Cup Winners' Cup disappeared, it is not only about the Champions League.
"If we can win a trophy, that represents a lot for Tottenham Hotspur's history as well and would be something really special."