Vachellia (formerly Acacia) trees are native to arid environments in Africa and the Arabian Peninsula, where they often support the local animal and plant communities acting as keystone species. The aim of this study was to examine whether oil pollution affected the central metabolism of the native keystone trees Vachellia tortilis (Forssk.) and V. raddiana (Savi), as either adults or seedlings. The study was conducted in the Evrona Nature Reserve, a desert ecosystem in southern Israel where two major oil spills occurred in 1975 and in 2014. Leaf samples were collected to analyze the central metabolite profiles from oil-polluted and unpolluted adult trees and from Vachellia seedlings growing in oil-polluted and unpolluted soils in an outdoor setup. We found that oil pollution had a stronger effect on one-year-old seedlings than on adult trees, reducing the levels of amino acids, sugars, and organic acids. While adult trees are mildly affected by oil pollution, the effects on young seedlings can cause a long-term reduction in the population of these keystone desert trees, ultimately threatening this entire ecosystem.