Hume sustained a hamstring injury during the international break with Canada and Mellor was replaced at half time in Preston's game with Walsall on Saturday after suffering damage to his ankle.
The duo have scored thirteen goals between them for the Lilywhites this season and Brown now has a selection headache for Wednesday's re-scheduled fixture.
"Iain has pulled his hamstring and he was a big miss at Walsall. At the moment there's a question mark about how long he's going to be out. I don't know Neil in terms of his recovery rates. Again, we'll have another look at him once things have settled down and we might get a better idea."
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