Belgium manager Roberto Martinez has suggested he will make many changes, with star names rested, and there has been a discussion in the country's media about finishing second and potentially avoiding Brazil in the quarter-finals. Belgium and England are equal on points and goal difference, which means if they draw, the group will be decided on disciplinary records. England are on top, having collected one fewer yellow card.
Asked whether he'd want to finish second, Southgate was emphatic.
"For our country, that would be a very difficult mindset to have. We want to win every game we go into. I don't know how we would go into a game not wanting to win and not wanting to play well. So I think that's dangerous territory if we start trying to plot and predict where we might end up. We had a really favourable draw, we all thought, in the last tournament [Euro 2016] and it didn't work out that way.
"I think we just have to keep playing as well as we can, keep preparing the team the right way, keep the momentum and I have to keep the squad involved. That's the one thing I think is really important."
Southgate is mindful of giving as many players in his squad the chance to play, not least because of his own experience as he, along with Martin Keown, was not used at the 2002 World Cup. Southgate has already fielded 16 players.
"I felt it was important for [Jamie] Vardy, [Fabian] Delph and [Danny] Rose, who have trained so well and been such an important part of the group as more senior players [to come on against Panama]," he said.
"There were four or five others I'd have liked to get on the pitch for that same reason. Balancing that with a couple of the younger ones was a difficult decision. I've got to think through all of those things, competition for places, players who need match minutes and keeping the unity of the squad."
Dele Alli's return to training yesterday following a thigh injury puts him in contention and it is likely Southgate will want to rest Jesse Lingard. Delph could also be in line to feature, while Marcus Rashford could replace Raheem Sterling and be given his first start.
Another expected starter is Eric Dier, with Jordan Henderson rested, while Gary Cahill should come into defence and Southgate will not risk Kieran Trippier if he has not recovered from the slight injury he felt against Panama.
Southgate will weigh up switching Ashley Young to right wing-back - the most likely option - or starting with Trent Alexander-Arnold, with Rose on the left. If all that happens, it would be six changes and what helps Southgate is that most of those players could be in his first XI in any case.