Lazio sit top of the 36-team standings after three games, and despite a sluggish start on the continent, Porto are now in supreme form themselves.
Match preview
In a peculiar piece of scheduling by Serie A, Lazio played as recently as Monday, but came through it unscathed, beating Cagliari 2-1 to move into fifth, three points off the summit.
Marco Baroni's side are in great form domestically, and they are also cruising through Europe at present, with three wins from three, and they have been in the lead for 80% of their Europa League games so far.
Along with Tottenham Hotspur and Anderlecht, Lazio still have a 100% record, and an impressive goal difference of plus-eight means they sit top.
The convincing manner of victory is what has been so impressive so far, from a club that has often limped its way through the early stages of European campaigns in recent years.
Home form played a crucial role in their early season form, as Baroni has now oversaw five straight wins at the Stadio Olimpico, contributing to a 13-game unbeaten run here for Lazio.
Across all venues, a 1-0 defeat at Juventus is the only game Lazio have failed to win in their last nine, illustrating the challenge facing visitors Porto here.
The Portuguese giants have a strong record against the Biancocelesti though, having never previously lost in four meetings.
With six wins in a row, 17 unanswered goals, and none conceded in over eight hours of action, Porto are one of the most in-form sides anywhere in Europe at present.
A stuttering start that saw Vitor Bruno's men lost to Sporting Lisbon and Bodo/Glimt across two competitions means they are still playing catch up - three points behind Sporting, and down in 15th in the Europa League.
The matchday three victory over Hoffenheim has moved them up the standings though, with Samu Omorodion playing an important role again with the clinching goal that moved him to the top of the Europa League scoring charts.
Porto have not faced any team in the form of Lazio at such a high level though, and the Dragons are often poor travellers to Italy, as in 12 previous trips to the country, Porto have won only once, but that did come in this stadium, against Lazio's rivals Roma back in August 2016.
Lazio Europa League form:
W
W
W
Lazio form (all competitions):
W
L
W
W
W
W
Porto Europa League form:
L
D
W
Porto form (all competitions):
W
W
W
W
W
W
Team News
Lazio captain Mattia Zaccagni overcame illness to come on as a late substitute and score the winner from the penalty spot in their 2-1 victory over Cagliari on Monday, and should be fit to start here.
Nuno Tavares sat that game out with suspension and will return, but Tijjani Noslin's matchday-one red card against Dynamo Kyiv means he will serve the final game of that ban here.
In defence, Manuel Lazzari made his first start in over six weeks on Monday, and could feature from the outset for the first time in this competition this season here.
Porto defender Zaidu Sanusi has continued his recovery from an ACL tear by featuring for the club's B team at the weekend, but the medical staff are still very cautious about including him in the first team.
Ivan Marcano remains out with the same injury, and left-back Wendell is also set to miss this encounter with a muscle problem.
After scoring two goals off the bench in the 4-0 win over Estoril at the weekend, Galeno is likely to come in out wide having started Porto's previous two European matches.
Lazio possible starting lineup:
Mandas; Lazzari, Gila, Romagnoli, Nuno Tavares; Vecino, Dele-Bashiru; Pedro, Dia, Zaccagni; Castellanos
Porto possible starting lineup:
Diogo Costa; Martim Fernandes, Perez, Tiago Djalo, Moura; Varela, Nico, Ivan Jaime; Pepe, Samu, Galeno
We say: Lazio 2-1 Porto
Both previous head-to-heads here at the Olimpico have ended in draws between Lazio and Porto, but the form of the home side will make them slight favourites.