Speaking at Friday's coronavirus briefing at Holyrood, the First Minister said the entire nation will be cheering Steve Clarke’s men as they take on the Auld Enemy in the Euro 2020 Group D clash.
Ms Sturgeon said: “The Scotland v England game at Wembley tonight will be a great occasion, at least we hope it will be a great occasion.
“Let me just briefly take this opportunity to wish, Steve Clarke, Andy Robertson and the whole of the team, the very very best of luck for the match tonight.
“All country will be cheering you on.”
Thousands of Scottish fans have descended on London as anticipation builds ahead of just the second ever major tournament meeting of international football’s oldest rivals.
But Scotland’s First Minister urged those in London, as well as fans staying north of the border, to take care while watching, particularly for those gathering in someone’s house.
“Remember to take the basic precautions, keep the windows open, wash your hands regularly and please be especially careful around people who are not yet fully vaccinated or who might be more vulnerable,” she said.
“And be careful if, or hopefully when, Scotland score some goals.”
She added: “I know these precautions are tiresome for everybody in every context and they’re particularly tiresome when people are trying to enjoy the normal pleasures of a football match.
“But this virus, it doesn’t care about football – it’s not a Scotland fan or an England fan, it only cares about spreading from one person to another.”
Ms Sturgeon went on to say she would “condemn and abhor” anti-English chants from football supporters at tonight’s match.
“I would abhor and condemn unreservedly any anti-English chants,” she said.
“Just as Scots we would not want to hear that coming from fans of any other country.
“Racism, xenophobia, anything like that, whether it’s a football context or in life generally is not to be tolerated.”