The ability to adjust skin darkness to the background is a common phenomenon in fish. The hormone alpha-melanophore-stimulating hormone (alphaMSH) enhances skin darkening. In Mozambique tilapia, Oreochromis mossambicus L., alphaMSH acts as a corticotropic hormone during adaptation to water with a low pH, in addition to its role in skin colouration. In the current study, we investigated the responses of this fish to these two environmental challenges when it is exposed to both simultaneously. The skin darkening of tilapia on a black background and the lightening on grey and white backgrounds are compromised in water with a low pH, indicating that the two vastly different processes both rely on alphaMSH-regulatory mechanisms. If the water is acidified after 25 days of undisturbed background adaptation, fish showed a transient pigmentation change but recovered after two days and continued the adaptation of their skin darkness to match the background. Black backgrounds are experienced by tilapia as more stressful than grey or white backgrounds both in neutral and in low pH water. A decrease of water pH from 7.8 to 4.5 applied over a two-day period was not experienced as stressful when combined with background adaptation, based on unchanged plasma pH and plasma alphaMSH, and Na levels. However, when water pH was lowered after 25 days of undisturbed background adaptation, particularly alphaMSH levels increased chronically. In these fish, plasma pH and Na levels had decreased, indicating a reduced capacity to maintain ion-homeostasis, implicating that the fish indeed experience stress. We conclude that simultaneous exposure to these two types of stressor has a lower impact on the physiology of tilapia than subsequent exposure to the stressors.