History suggests that it would be difficult but not impossible for Labour to win.
As I noted earlier this week, the Scottish independence referendum is win-win for the Conservatives. If Scotland votes No, the Union is saved, if Scotland votes Yes, the Tories win a huge advantage over Labour. While Ed Miliband's party would be stripped of 41 MPs, David Cameron's would lose just one. This has prompted some to suggest that an independent Scotland would leave the Tories with an inbuilt "permanent majority".
But how true is this? Without Scotland, Labour would still have won in 1997 (with a majority of 139, down from 179), in 2001 (129, down from 167) and in 2005 (43, down from 66). What those who say that Labour cannot win without Scotland are really saying is that they do not believe Labour can ever win a sizeable majority again. This may or may not be true but it's a different debate. History suggests that England and Wales alone are capable of electing a Labour government when the conditions are right.
What is true is that so long as British politics remains "hung", Labour cannot afford for Scotland to go it alone. Were it not for Miliband's Scottish MPs, the Tories would have won a majority of 19 at the last election. The loss of Scotland, coupled with the coalition's boundary changes (which will deprive Labour of 28 seats, the Tories of 7 and the Lib Dems of 11), would stack the odds against a Labour majority.
Should Scotland win independence, one likely consequence is that Labour will shift to the right in an attempt to win greater support from English voters, who are generally perceived to lie to the right of their Scottish counterparts (although psephology paints a more complex picture). Thus, those who want Labour to win again and to do so on a social democratic programme have every interest in preserving the Union.