Manchester City must overturn a first-leg deficit on home soil against Premier League opposition for the second season running in the Champions League quarter-finals as they welcome Tottenham Hotspur to the Etihad Stadium.
That was perhaps down to Guardiola knowing the result of the first leg would not prove decisive. City also have the Premier League and FA Cup to focus on, having already wrapped up the EFL Cup, so last week's match was his best opportunity to rotate slightly.
The pressure is now very much on for the return fixture, though, with Man City needing to score to keep alive their quadruple hopes.
Of the 32 previous occasions of a side losing the first leg of a two-legged Champions League tie 1-0 away from home, 10 have gone on to progress (31%). That is not a tiny number - certainly not small enough to suggest that Tottenham can start preparing for the semi-finals.
Guardiola will also be aware that his side are in a far better position in this season's quarters compared to 12 months ago when trailing Liverpool 3-0 from the first leg. City needed just two minutes to open the scoring in the second leg, but some key decisions went against them and they lost 2-1 on the night, 5-1 on aggregate.
Their latest European disappointment was softened somewhat by their astonishing Premier League campaign that saw them break into triple figures in terms of points. A year on, though, they do not have that as a safety net, with Liverpool pushing them all the way.
Wednesday is all about doing what they could not last season by overturning a first-leg deficit against a domestic rival. City will feel confident of picking up a win in front of their home supporters, having won 23 of their 25 matches in all competitions at the Etihad Stadium this season.
However, they have lost two of their last three home games in the Champions League knockout stages, winning the other 7-0 against Schalke in this season's last 16. Repeat that performance from last month and a place in the semis will be theirs, but Tottenham will certainly not make life easy for them as they aim to strike the first major blow on their rivals' campaign.
Recent form in Champions League: WDWWWL
Recent form (all competitions): WWWWLW
While their domestic campaign fell apart in the space of a month with four defeats in seven such fixtures between January 24 and February 27, Tottenham's European campaign has gone from strength to strength.
The Lilywhites, like City, were still just about in contention for a quadruple prior to an EFL Cup defeat to Chelsea, an FA Cup exit to Crystal Palace and losses to Burnley and Chelsea in the Premier League.
Now all of their eggs are very much in one basket, albeit with a top-four finish still being important to the club's long-term aspirations, meaning an aggregate loss to City on Wednesday will all but end their campaign.
Tottenham produced a brilliant turnaround in the group stage to even make it as far as the knockouts, taking seven points from their last three matches against PSV Eindhoven, Inter Milan and, most impressively of all, Barcelona to join the Catalan giants in the round of 16.
With positive results under their belt from trips to Dortmund (twice), Juventus and Barcelona over the last two seasons, this visit to the Etihad Stadium - hardly a fortress in European competition - will not faze Mauricio Pochettino.
However, their win at Dortmund in early March is the only time Tottenham have avoided defeat in their last seven away matches, including a penalty defeat to Chelsea in the EFL Cup semi-finals.
A goalless draw will be enough to see them through on Wednesday, though, and a 1-0 loss will also be enough to force extra time, so Pochettino - learning from those losses to the likes of Palace, Burnley and Southampton - can set out his side differently.
The stakes could not be any higher, explaining why Pochettino described the first leg - and subsequently the return match - as the biggest of his managerial career. The job half done, Poch and his players are potentially 90 minutes away from the biggest result of their lives.
Recent form in Champions League: WLLWWW
Recent form (all competitions): WWDWWW
Son is expected to start through the middle in Kane's absence, though, and Lucas Moura may also have forced his way into Pochettino's plans after netting a hat-trick on Saturday.
As for the hosts, they seem certain to recall De Bruyne, but Guardiola has overlooked Sane more often than not for these big matches of late.
Influential holding midfielder Fernandinho missed the Palace match with a muscle injury but should be fine to play a full part in this one, while Bernardo Silva returned to action with 25 minutes at Selhurst Park.
Elsewhere, Aguero is likely to get the nod over Gabriel Jesus and Oleksandr Zinchenko is in contention to replace Fabian Delph at left-back, assuming Guardiola does not fancy taking a risk on a not-yet-fully-fit Benjamin Mendy.
Manchester City possible starting lineup:
Ederson; Walker, Otamendi, Laporte, Zinchenko; De Bruyne, Fernandinho, D.Silva; Bernardo, Aguero, Sterling
Tottenham Hotspur possible starting lineup:
Lloris; Alderweireld, Sanchez, Vertonghen; Trippier, Sissoko, Winks, Rose; Eriksen, Lucas; Son
Head To Head
In 157 competitive meetings between these two sides, both have recorded 61 wins and there have been 35 draws, though City had won three in a row before their first-leg defeat last week.
This season's Premier League meeting at Wembley Stadium ended in a 1-0 win to the Citizens thanks to an early Riyad Mahrez goal, with the reverse fixture scheduled for this Saturday.
In English domestic knockout football, the Lilywhites have won nine of the teams' 14 ties – including five of the last six.
We say: Manchester City 1-0 Tottenham Hotspur (1-1 agg, Spurs through on pens)
Tottenham have won each of their last three Champions League matches - never before have they won four in a row in the competition - and Man City have lost all five of their previous European matches against fellow English clubs, including all three in the Champions League. The Citizens may be considered the favourites with the bookies, but Pochettino's men will be confident of creating some personal history.