There seems to be no reason why not.
On page 215 of the Player's Handbook it says:
Some one-handed weapons are light enough for you to use in your off
hand while holding another one-handed weapon in your other hand.
The suggestion seems to be that an off-hand weapon is simply one that you are capable of wielding in your non-dominant hand while simultaneously holding one in your main hand, not that you cannot hold an off-hand weapon in that hand unless you are wielding one in your main hand.
Consider sheathing weapons. If you cannot wield a weapon in your off hand if you main hand is free, and you are duel-wielding, you cannot sheath or drop your main weapon without simultaneously sheathing or dropping your off-hand weapon.
The one snag I can find is based on semantics - what counts as the main hand seems to be entirely defined as the hand you wield your weapon in, and the off-hand is the hand you are not wielding your main weapon in.
The Rules Compendium gives:
One-Handed: A one-handed weapon is light enough or balanced enough to
wield in one hand. A creature can carry a one-handed weapon in each
hand, but doing so does not let the creature make extra attacks in a
round. The creature must choose which of the weapons it is wielding
when it makes a weapon attack. If a weapon attack power allows the use
of two weapons, one of the weapons must have the off-hand property.
Note that it does not specify that the off-hand weapon must be in your off-hand, just that one of them must be an off-hand weapon. This suggests the designation of main and off hand is entirely arbitrary, especially as you can then choose which weapon you are 'wielding'.