This work aims to assess the influence of environmental stress in the middle course of the Comoé River on the morphological characteristics of Oreochromis niloticus populations using the geometric morphometric approach. A total of 248 specimens of O. niloticus were collected from four sites (M'Basso, YèrèYèrè, Abradinou and Bettié). No specimen of O. niloticus has been collected from the Manzan River, which has a high level of gold panning activity. Nineteen (19) homologous landmarks were digitized on each individual. Data were studied using principal component analysis, canonical variable analysis, discriminant function analysis and allometric analysis. The PC1 and PC2 axes show an extension of the deformation grids at the level of the head and the caudal and dorsal fins. However, the PC3 axis almost exhibits a deformation grid that deforms at the caudal fin, pectoral fin, and dorsal fin. The results of the various analyzes showed significant differences between the morphology of the populations studied. These differences were observed mainly in the head, dorsal and pectoral fins. The disturbance of aquatic habitats has an impact on the morphology of specimens of O. niloticus from the middle course of the Comoé River. A slight deformation is recorded in the individuals of O. niloticus at M'Basso, considered the least disturbed site. On the other hand, a strong deformation is observed in specimens from the YèrèYèrè, Abradinou and Bettié sites which are more disturbed.