This study sought to investigate in situ oxygen isotopes (δ18O) within alluvial colorless-white to blue sapphires from the Orosmayo region, Jujuy Province, NW Argentina, in order to provide additional constraints on their origin and most likely primary geological environment. Analyses were conducted using the in situ SIMS oxygen isotope technique on the same grains that were analyzed for their mineral inclusions and major and trace element geochemistry using EMPA and LA-ICP-MS methods in our previous study. Results show a significant range in δ18O across the suite, from +4.1% to +11.2%. Additionally, akin to their trace element chemistry, there is significant variation in δ18O within individual grains, reaching a maximum of 1.6%. Both the previous analyses and δ18O results from this study suggest that these sapphires crystallized within the lower crust regime, involving a complex interplay of mantle-derived lamprophyres and carbonatites with crustal felsic rocks and both mantle- and crustal-derived metasomatic fluids. This study reinforces the importance of the in situ analysis of gem corundums, due to potential significant variation in major and trace element chemistry and ratios and even oxygen isotope ratios within discrete zones in individual grains.