The fall armyworm (FAW), Spodoptera frugiperda (Lepidoptera: Noctuidae), is a significant invasive pest that has recently expanded to many countries worldwide. It is a polyphagous pest, destroying almost all vegetables and numerous commercial agricultural crops worldwide. The purpose of the current study was to compare between the efficacy of a newly isolated local strain of entomopathogenic nematodes (EPNs), Steinernema coded as (15) and the foreign strain S. carpocapae (All) against 3^rd larval instar of S. frugiperda under laboratory conditions with four concentrations (5, 10, 20, and 40 infective juveniles IJs/ml/larvae). Our results revealed that the newly local strain recorded the maximum larval mortality, reaching 100%, while the foreign strain caused 91.67% larval mortality at concentration (40 IJs/ml) after 72 hr. of treatment. Our results showed that the relative potency of the newly local strain was 1.98 more potent than the foreign strain. By studying the effect of LC₅₀ (4.4778 IJs/ml) of the newly isolated local strain of EPN on biochemical aspects of larval haemolymph such as total protein and some enzymes activity. Results showed that the treated larvae had lower protein content in compared to control. In addation, the activity of enzymes (phenoloxidase (PO) and carboxylesterase (CarE)) was affected by newly local strain treatment. In other way, (PO) and (CarE) enzymes activities were increased significantly in treated larvae in compared to control.