At this early stage, much of the legitimacy of Islam is its military success and the ability to pay its members what it could pillage and conquer. Because Islam prevented the Arab tribes from attacking each other, more or less they had to attack non-Muslims instead. The Arabs are still bedouin raiders, and if they are going to fight, they need to be paid in booty. And if they can't get booty from non-Arabs, they are going to go back fighting themselves for such goods.
A major defeat this early could cause a significant number of tribes to apostatize once again. And depending on how many devout Muslims died, and if Khalid himself died, it might be hard for the core Muslim group to reconquer them. If the Muslims can unit the arabs once again, they are going to need to attack Byzantium and Persia again.
Of course, this assumes that Khalid suffered a crushing defeat at Yarmouk that allowed the Byzantines to drive them out. By this time Khalid had already conquered most of Palestine, Jordan, and southern Syria, and the Muslims controlled much of Mesopotamia as well. A defeat that kept most of the Muslim army in the field would probably mean the war would continue as Byzantines attempted to reconquer the lands lost to Khalid while the Persians attacked the Muslims in the east. It is just as easy to see the Muslim forces regathering and win its subsequent battles as it would with Muslims losing everything. Khlaid was an extremely good general. In which case, the loss at Yarmouk would probably be seen as "Allah humbling the pride of the Muslims to make them more worthy of victory" or a similar ex post rationales.
So everything depends on how big a victory the Byzantines get at Yarmouk and whether Khalid survives.