Stress is a condition in which the body homeostasis is perturbed by various stimuli such as sickness and psychological stimuli. Stress evokes adaptive responses including febrile, neuroendocrine, and behavioral responses. Prostaglandin (PG) E(2) is a metabolite from arachidonic acid, and exerts its functions through G-protein-coupled receptors called EP1, EP2, EP3, and EP4. Recent studies using knockout mice and selective drugs revealed the roles of these receptors in stress responses. Upon sickness, PGE(2) mediates fever through EP3, while both EP1 and EP3 are involved in ACTH release. In addition, EP1 controls impulsive behaviors under psychological stress through the dopaminergic system. PGE(2) produced by various cell types may integrate multiple stress stimuli through PGE receptor subtypes for adaptive responses.