Liverpool's Daniel Sturridge made his first start in 573 days for England on Tuesday night, with James Milner also captaining his country for the first time, as they lost 2-1 to Netherlands at Wembley Stadium.
Adam Lallana was also in action, starting in attacking midfield, slightly ahead of Milner and behind a pairing of Sturridge and Leicester City striker Jamie Vardy, with Nathaniel Clyne and Jordan Henderson also on the bench.
Four Reds all feature in disappointing home defeat
After a largely dull and ponderous first-half, Vardy's second goal in as many games broke the deadlock following a sublime team move in which all of Milner, Sturridge and Lallana were involved.
Sprinting down the left side, Milner collected Everton defender John Stones' pass before rolling a ball across the box which Sturridge dummied, allowing Lallana to pick up possession and play a perfectly-weighted pass into Kyle Walker down the inside-right channel. His pull-back found Vardy for a sidefooted finish from 10-yards out, putting England ahead in eye-catching fashion.
But only five minutes into the second-half, Netherlands levelled through Vincent Janssen, who crowned his first start with a first international goal, despatching a spot-kick after Danny Rose was accused of a handball inside his own area.
Sturridge was withdrawn after 58 minutes after his first national team appearance since September 2014, whilst clubmate Clyne replaced Rose for the Three Lions, before Lallana later went off for Harry Kane with 20 minutes remaining.
Not long after, a controversial refereeing decision, with Spanish official Antonio Mateu Lahoz failing to call for a foul when Janssen bundled over substitute Phil Jagielka, saw the striker set up Luciano Narsingh for a simple finish to make it 2-1.
With the Reds' other two starts both subbed off and despite having not played in the previous game three days' earlier, Milner was withdrawn for Dele Alli on 81 minutes - but the changes could not help Roy Hodgson's men find a goal to retrieve a draw as they suffered only a second defeat in their last 18 games.
Sakho, Skrtel and Can all involved across Europe
Elsewhere on Tuesday, France defender Mamadou Sakho played for the full game as the 2016 UEFA European Championships hosts beat Russia 4-2 in impressive fashion in an emotional evening at the Stade de France, their first game there since the horrific Paris attacks in November.
Martin Skrtel was also in action as he took up a berth in central defence against Republic of Ireland in Dublin, conceding a penalty kick in the first-half before they went on to draw 2-2, whilst Marko Grujić didn't make his senior international debut for Serbia, remaining on the bench in a 1-0 win over Estonia.
Simon Mignolet was also an unused substitute as Belgium lost 2-1 to Portugal whilst Emre Can, having played the full game in Germany's loss to England on Saturday, came on for the final 20 minutes of his country's convincing 4-1 win over Italy from the bench. Reported Liverpool transfer targets Mario Götze and Jonas Hector were both on the scoresheet.
Allen captains country and Smith stars on Monday
The night before, Joe Allen played 90 minutes and even donned the armband for the second-half, starring as his country's best player as Wales lost 1-0 in Kiev against Ukraine - with back-up goalkeeper Danny Ward an unused sub after his first cap against Northern Ireland last week.
Brad Smith was also in action, featuring for 90 minutes in his fifth cap for Australia as they beat Harry Redknapp's Jordan 5-1 to secure their place in the third stage of qualifying and keep their dreams of reaching the 2018 FIFA World Cup alive.
Allen, Ward and Smith have all return to Merseyside, to be joined by their fellow international clubmates in the coming days, and will resume training ahead of the Reds' Premier League clash with Tottenham Hotspur at Anfield on Saturday evening.
Meanwhile, Jürgen Klopp is still waiting to learn the full extent of injuries to Roberto Firmino, Divock Origi and Christian Benteke, all of whom dropped out of international duty over the two-week break due to hamstring, thigh and knee injuries respectively.
Only Philippe Coutinho remains on international duty, with his Brazil side facing Paraguay in another World Cup qualifier on Wednesday night. Given that he only came off the bench to play 20 minutes of their first game, a 2-2 draw with Uruguay, he is likely to feature again.
It is hoped that Coutinho, alongside all the rest of the Reds' internationals, will return unscathed as Liverpool look to end the season strongly in the league and reach the semi-finals of the UEFA Europa League, with a mouthwatering two-legged affair with Borussia Dortmund to come in a few weeks' time.