The relation between copper alginate fibers and immunotoxicity in animals was studied by dividing guinea pigs and mice into control groups and experimental groups. Varied weights of fibers were subcutaneously embedded in the experimental groups, whereas the control groups were operated on simulatively. Morphology analysis, erythrocyte osmotic fragility (EOF) test, direct plaque-forming cell (PFC) assay, quantitative hemolysis spectrophotometry (QHS) assay, macrophages phagocytosis assay, and pathology analysis were used to examine morphology, microstructure, and immunotoxicity. With increasing doses of copper alginate fibers, the EOF of experimental groups increased in contrast with the control group. Moreover, the antibody level decreased based on the results of the PFC and QHS assays, and macrophages phagocytosis descended in relation to dose. However, the immune functions were weakened without time dependence. According to pathologic photographs, the partial organs were damaged, implying bad histocompatibility. Hence, copper alginate fiber is proved to be a harmful material for medical devices.