David K. Randall explains how the rigid 8:30pm timing of Monday Night Football leaves teams vulnerable to their circadian rhythms, particularly in that "strength, flexibility, and reaction times surge in the early evening, when [they pull] the body out of the post-lunch funk":

The scheduling of Monday Night Football games presents a unique circadian problem, especially if a team from the West Coast is playing a team from the East Coast. Players on the West Coast team are playing at their equivalent of 5:30 p.m..., [while East Coast players'] bodies are past their natural performance peaks before the first quarter ends. By the fourth quarter, the team from the East Coast will be competing close to its equivalent of midnight. Their bodies will be subtly preparing for sleep by taking steps such as lowering the body temperature, slowing the reaction time, and increasing the amount of melatonin in their bloodstream. Athletes on the team from the West Coast, meanwhile, are still competing in the prime time of their circadian cycle.

The trend bears out historically, it seems - with surprisingly consistent odds: