The present study aimed to evaluate the effects of different waterborne sublethal concentrations of Ag-NPs LC (96h) on common carp Cyprinus carpio using a multi-biomarker approach. Fish (9.22 ± 0.12 g) were stocked in fiberglass tanks and exposed to concentrations of 0 (control), 12.5%, 25% and 50% of Ag-NPs LC (96h) or Ag-NO LC (96h), as the source of Ag ion, for a period of 21 days. At the end of study, tissue Ag contents were significantly (P < 0.05) higher and different in fish exposed to concentrations of 25% and 50% compared to the control. The numbers of RBCs, hematocrit, and MCHC values at these concentrations differed significantly in respect to the control. No significant effects were observed for hemoglobin, MCH, and MCV values. The number of WBCs was significantly higher at concentrations of 12.5% and 25% compared to the control. Meanwhile, the percentage of neutrophils significantly elevated at concentrations of 25% and 50%. Serum total protein at concentration of 50% detected significantly lower than that of 12.5% or the control. The serum albumin and globulin levels significantly declined in Ag-NPs-exposed groups versus the control. The serum ACH50 and total immunoglobulins showed significantly lower values in the treatments of 25% and 50% compared to the control. The serum glucose, cortisol, ALT, and ALP values significantly escalated upon Ag-NPs exposure. The serum SOD and CAT showed enhanced activity in the treatment of 12.5% vice versa significantly diminished at concentrations of 25% and 50% compared to the control. The exposure to the concentrations of 25% and 50% significantly dwindled the lysozyme activity and total immunoglobulin levels in skin mucus. In conclusion, sublethal concentrations of Ag-NPs LC (96h) impaired fish health status at higher concentrations and 12.5% of Ag-NPs LC (96h) was presumably safe for common carp aquaculture.Copyright © 2020 Elsevier Inc. All rights reserved.