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We present the first high-resolution abundance study of ESO 280-SC06, one of the least luminous and most metal-poor gravitationally bound Milky Way globular clusters. Using Magellan/MIKE spectroscopy for ten stars, we confirm the cluster’s low metallicity as [Fe/H] = $-2.54\pm 0.06$and the presence of a nitrogen-enhanced star enriched by binary mass transfer. We determine abundances or abundance upper limits for 21 additional elements from the light, alpha, odd-Z, iron peak, and neutron-capture groups for all ten stars. We find no spread in neutron-capture elements, unlike previous trends identified in some metal-poor globular clusters such as M15 and M92. Eight of the ten stars have light-element abundance patterns consistent with second-population globular cluster stars, which is a significantly larger second-population fraction than would be expected from the low present-day mass of ${10}^{4.1}$Msun. We estimate the initial mass of the cluster as ${10}^{5.4-5.7}$Msun based on its orbit in the Milky Way. A preferential loss of first-population stars could explain the high fraction of second-population stars at the present time. Our results emphasize the importance of considering mass loss when studying globular clusters and their enrichment patterns.