Lumpy skin disease (LSD) is a viral disease of cattle, characterised by the formation of nodules in different parts of the body. In this study, it was conducted to assess the pattern of changes of albumin, tumour necrosis factor-alpha (TNF-α), haptoglobin (Hp), serum amyloid A (SAA) and neopterin levels in cattle with LSD, to assess the clinical course of the disease, and to the demonstration of inflammatory process in cattle with LSD. This study was carried out in 30 cattle, including 20 animals naturally infected with LSD and 10 healthy animals. It was determined that, in the cattle infected with LSD, while albumin concentrations had significantly decreased (P=0.004) in comparison to the control group, Hp (P<0.001), SAA (P<0.001) and neopterin (P<0.001) concentrations had significantly increased. Receiver operating characteristic (ROC) curve was used to calculate the sensitivity and specificity of Hp, SAA and neopterin. The cut-off values of the healthy and infected cattle for Hp, SAA and neopterin were determined to be 0.196 mg/mL, 41.38 μg/mL and 23.93 nmol/mL, respectively. At these cut-off values, high levels of sensitivity (85% for Hp, 95% for SAA and 70% for neopterin) and specificity (90%) were detected. It was determined that SAA levels were of higher sensitivity and specificity compared to Hp and neopterin levels with respect to the demonstration of inflammation associated with LSD. Furthermore, the clinical picture of the disease was found to be significantly correlated with the Hp, SAA and neopterin levels.