Crustaceans’ endocrinology is a vastly understudied area of research. The major focus of the studies on this topic to date has been related to the molting cycle and in particular, the role of crustacean hyperglycemic hormone (CHH), as well as the role of other hormones in facilitating physiological phenotypic adjustments to salinity changes. Additionally, while many recent studies have been conducted on the acclimation and adaptation capacity of crustaceans to a changing environment, only few have investigated internal hormonal balance, especially with respect to an endocrine response to environmental change. The current study hence aimed to identify and characterize endocrine components of acid-base regulation in the European green crab, Carcinus maenas. We show that both the biogenic amine octopamine (OCT) as well as CHH are regulatory components of branchial acid-base regulation. While OCT suppresses branchial proton excretion, CHH seemed to promote it. Both hormones were also capable of enhancing branchial ammonia excretion. Furthermore, mRNA abundance for branchial receptors (OCT-R), or G-protein receptor activated soluble guanylate cyclase (sGC1b), are affected by environmental change such as elevated pCO2 (hypercapnia) and high environmental ammonia (HEA). Our findings support a role for both OCT and CHH in the general maintenance of steady-state acid-base maintenance in the gill, as well as regulating the acid-base response to environmental challenges that C. maenas encounters on a regular basis in the habitats it dwells in and more so in the future ocean.