United and City are among the four Premier League clubs who have made it into the hat for the last-eight draw which takes place on Friday.
But with seedings no longer in place in the Champions League from the quarters onwards, it raises the prospect of both Manchester rivals being drawn to play home matches in the same week.
But Manchester police and the local authority say it is impossible for the city to host two European ties on consecutive days, meaning one would have to switched.
And Uefa regulations dictate the it is the club who finished higher in the league the previous year who would take precedence.
That means City, Premier League winners last season, would stay playing on the allotted dates they are drawn leaving United having to switch.
A Uefa statement said: "Manchester City and Manchester United will not be able to play at home on the same night, nor on consecutive nights, following a decision made by the relevant local authorities."
The first legs of the last-eight ties will be played on April 9/10 with the second legs the following week.
Being unseeded, there is the real prospect that two English sides will be drawn to face each other as the Premier League dominates Europe's top competition this season.
All would be looking to avoid each other, with Porto and Ajax – despite their heroics beating Real Madrid – being the preferred opponents.
Friday's draw will also determine who faces who in the semi-finals, so the path through to the final in Atletico Madrid's stadium in May will be laid out before each side.
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