UCL: Five major things to look out for as Chelsea,  Manchester United set for action

The second set of UEFA Champions League round of 16 first legs offers up a host of potential headline-makers, intriguing sub-plots and players to keep a close eye on.

LOSC look to upset holders Chelsea

LOSC Lille could scarcely have been handed a tougher assignment in only their second appearance in the round of 16. Holders Chelsea may have suffered a recent dip in the Premier League, but their European juggernaut has shown little sign of slowing. Their Ligue 1 opponents are in unfamiliar if previously charted territory, having been condemned to a 2-0 aggregate defeat by Manchester United in 2006/07.

To have any chance of springing a surprise, LOSC will surely need to do what has eluded so many – find a way past Edouard Mendy. The Chelsea keeper has kept four clean sheets in five UEFA Champions League games this season and 13 in 17 overall.

Villarreal and Juventus meet for first time

Villarreal and Juventus are the only round of 16 opponents never to have met before. The Yellow Submarine have made it this far only twice previously, winning on each occasion before latterly suffering elimination at the hands of Arsenal. Their first appearance in 13 years also pits them against venerable opponents, the Old Lady appearing in the knockout stage for the eighth season running and the 18th time overall.

Away goals rule abolished

The away goals rule has been scrapped for the 2021/22 campaign. This means that ties in which the two teams score the same number of goals over the two legs go straight to two 15-minute periods of extra time. If the teams score the same number of goals, or no goals, during extra time, a penalty shoot-out is required.

Juve have lost their last two ties on away goals, however, against Lyon in 2019/20 and Porto last season. Just as Villarreal know they can't come up against their bogey team the Gunners, the Bianconeri can at least be sure of not suffering the same away-goals fate this time around.

Ronaldo out to breach Atlético's fortress

Atlético's record in Madrid in the UEFA Champions League knockout stage is quite remarkable – 14 games since 1997, nine wins and no defeats. If anyone can scale the Estadio Metropolitano rampart, however, it is surely Cristiano Ronaldo, who has scored 25 career goals against Atleti, including in extra time of the 2014 final and during the shoot-out of the 2016 showpiece.

Ronaldo's influence for United this season has arguably been matched only by David de Gea at the other end of the pitch. The Spain keeper has been in sensational form and is sure to want to pull out all the stops when he faces his former side for the first time.

Can Haller keep his scoring run going?

Benfica vs Ajax is one of only two ties – along with Inter vs Liverpool – pitting together two former winners. Erik ten Hag's Ajax look to be a vintage model, racking up six group stage wins out of six thanks to a fluent, fluid, possession-based style of football.

The man crossing the Ts and dotting the Is at the top end of the pitch has been Sébastien Haller, the first player ever to score ten goals in his first six UEFA Champions League matches, and only the second – after Cristiano Ronaldo, no less – to find the net in all six group games. How much longer can he keep the sequence going?