Ryan Giggs says Manchester United must deliver an immediate response against Fulham on Saturday after opening their Premier League title challenge with a lacklustre defeat at Everton.

While champions Manchester City underlined their determination to hold onto the title with a come-from-behind win over Southampton and Chelsea – inspired by new signing Eden Hazard – swept to the top of the table with wins over Wigan and Reading, Sir Alex Ferguson’s United are pointless thanks to their tepid display at Goodison Park.

United can ill afford to fall six points behind City and Chelsea even at this early stage, but Giggs is confident the Everton defeat will serve as a wake-up call for his team-mates.

“It wasn’t a nice feeling to lose the title last season – it never is, but it was the manner in which we lost it which was tough to take,” Giggs said.

“I’m sure if we put that much effort in again and get that little bit of luck then we’ll go that extra step.

“The van Persie signing sends out a big message. And it’s great when a player comes out and says he wants to come to the club as well.”

Ferguson could hand van Persie his first start on Saturday, while Jonny Evans should return from injury to ease United’s defensive injury crisis.

If United do see off Fulham at Old Trafford, it will give City’s trip to Liverpool 24 hours later even greater significance.

City will be without Argentina striker Sergio Aguero as he recovers from a knee injury suffered against Southampton and boss Roberto Mancini will hope the Argentine’s absence doesn’t expose the club’s failure to sign a new striker.

Mancini, who wanted to buy van Persie from Arsenal, has been frustrated by City’s lack of transfer success and, with Aguero out, he has the difficult task of keeping the unpredictable Carlos Tevez fully focused on leading the attack.

Chelsea head into their home clash against Newcastle in buoyant mood after going top of the table for the first time in 21 months.

Chelsea finished a disappointing sixth place last term.

On Sunday, Arsenal travel to Stoke looking to lift the gloom around the north London club since van Persie’s departure.

Arsene Wenger’s side were held to a 0-0 draw by Sunderland last weekend, prompting fears the Gunners would suffer the same kind of dismal run that followed the departures of Cesc Fabregas and Samir Nasri 12 months ago.