Abstract <p><i>Myxobolus cerebralis</i> (Hofer, 1903), a myxosporean parasite, is the etiological agent of whirling disease in salmonids, which is responsible for high mortality and significant economic losses in rainbow trout (<i>Oncorhynchus mykiss</i>) populations. Тhis investigation was conducted to establish the blood biochemical changes caused by <i>M. cerebralis</i> in rainbow trout and fill the gaps from insufficient studies on the changes in blood parameters. Furthermore, the investigation aimed to identify the negative effect of <i>M. cerebralis</i> on some key physiological parameters to monitor its effects on the animal’s metabolism. The infection was confirmed by clinical, histopatological and qPCR screening. Histopathological changes were observed in the vertebrae, brain, gills, eyes, and muscles of the infected fish. The infection was confirmed by clinical, histopatological and qPCR screening. Histopathological changes were observed in the vertebrae, brain, gills, eyes, and muscles of the infected fish. Mononuclear inflammatory cells were determined around ossifying and cartilage tissue of the vertebra; hyperplasia of the retina and giant cell-like structures in the granular brain tissue were also observed. Levels of total protein, globulins, cholesterol, alkaline phosphatase, and cortisol were greater than normal, while levels of creatinine, uric acid, albumin, calcium, and prolactin were lower than references for the species.</p>