Here is a pair of optional rules for GURPS. It's totally untested, and it will have a strong effect on a campaign. I'm just not sure how much because they have not been tested.
Fatigue Reduced Resistance
Fatigued characters are not only tired, but are less likely to resist disease, hostile spells, and their own internal disadvantages. In addition to the effects listed on p. B426, add the following:
Less than 1/3 your FP left As written, but also self-control rolls are one level worse - (15) becomes (12), (12) becomes (9) . . . and (6) allows success only a 3 or 4! Resistance rolls are at -3.
Fatigue Reduced Damage
Normally low FP reduce ST but do not affect calculated stats such as HP and damage. Optionally, when ST is halve because of low FP, it does affect damage.
Less than 1/3 of your FP left - a written, except ST-based damage is also halved. Roll damage normally, then halve it, rounding down. You can spend 1 FP in order to swing a full-strength blow, but this is a slippery slope down!