Lumpy skin disease is an infectious disease affecting the bovines and caused by Lumpy skin disease virus (LSD virus; LSDV). It is considered an endemic disease in African continent and was recorded in Egypt since 1988. This study aimed to monitor the cattle health condition along the course of the disease through the estimation of biochemical parameters. Besides, investigations on the incriminated strains of LSD virus circulating during outbreak in summer 2019 were performed. One hundred and eighteen cattle of different ages and sex were examined for LSD in some villages of Menoufia Governorate, Egypt. The clinical signs were recorded, and blood chemical analyses were applied on the infected animals. Conventional PCR was used to identify the LSDV using two conservative genes, fusion and P32 coding genes. The infected animals showed typical symptoms of the LSDV infection. Morbidity rates in cattle were high in males (43%) and in 6–12 months of age (44.4%). The hemogram showed significant (P < 0.05) decrease in the count of red blood cells (RBCs) (6.13 ± 0.51× 106/µl), hemoglobin (Hb) (9.07 ± 0.15 g%), hematocrit (HCT) (17.47 ± 0.48%), mean corpuscular volume (MCV) (41.77 ± 0.79fL), mean corpuscular hemoglobin (MCH) (13.53 ± 0.29Pg), and mean corpuscular hemoglobin concentration (MCHC) (30.43 ± 0.53g/dL) in infected animals compared with control. The leukocytes showed significant (P < 0.05) increase in the count of white blood cells (WBCs) (15.13 ± 0.03 x103/μl), lymphocyte (LYM) (7.17 ± 0.12 x103/ μl), monocytes and some eosinophil (MID) (2.93 ± 0.08 x103/ μl), and granulocytes (GRAN) (5.03 ± 0.09 x103/ μl) in infected animals. Serum biochemistry of the infected animals showed significant (P < 0.05) increase in all biochemical parameters except serum albumin (2.61 ± 0.35g/dL). Lumpy skin disease virus was detected by Polymerase chain reaction (PCR) for both genes and the sequences of the fusion and P32 proteins were deposited in the GenBank by the accession numbers MN699855 and MN699856, respectively. Thus, attention should be directed to the circulating LSDV strain in the field and comparing it with the previously isolated strains. Field practitioners should depend on the blood parameters of the infected animals to select the appropriate remedies.