The saw-scaled viper (Echis carinatus carinatus) is a major venomous snake in Sri Lanka (SL) responsible for massive numbers of snakebites on the island; nevertheless, its venom proteome composition has never been explored. The proteome composition of SL E. c. carinatus venom (SL ECV), revealed by tandem mass spectrometry analysis, showed that it is composed of 42 enzymatic and nonenzymatic proteins belonging to 12 snake venom protein families. Snake venom metalloproteases (SVMP) and snaclec comprised the most abundant enzymatic and nonenzymatic proteins, respectively. When the composition of SL ECV was compared to the previously determined venom composition of Southern India ECV (SI ECV), 16 proteins were found in common. The SL ECV proteome composition was correlated with the clinical manifestations and pathophysiology of E. c. carinatus envenomation in SL. Polyvalent antivenom (PAV) raised in equine against the "Big Four" venomous snakes of India is typically exported to SL for snakebite treatment; however, the poor immunological cross-reactivity, partial in vitro neutralization of enzymatic activities, and some pharmacological properties, mostly shown by low molecular mass toxins (25 kDa) of SL ECV by Indian PAVs are major concerns for the effective treatment of ECV envenomation in SL.