The 7.30pm kick-off sees the two teams contesting the Doddie's Club Trophy, with Scottish great Doddie Weir having spent the majority of his playing career at Melrose and Newcastle.
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Newcastle Falcons director of rugby Dean Richards said: "We have always been keen to help Doddie's charity with their great work funding research into motor neurone disease, and would urge as many people as possible to come along and support this fixture.
"We played Southern nights at home for the cup a couple of years ago, and were always keen on doing so again. With having a bye week in the Gallagher Premiership this seemed like the perfect time to do it, and it should be a good game for an outstanding cause."