Larger benthic foraminifera (LBF) are unicellular eukaryotic calcifying organisms and an important component of tropical and subtropical modern and ancient oceanic ecosystems. They are major calcium carbonate producers and important contributors to primary production due to the photosynthetic activity of their symbiotic algae. Studies investigating the response of LBF to seawater carbonate chemistry changes are therefore essential for understanding the impact of climate changes and ocean acidification (OA) on shallow marine ecosystems. In this study, calcification, respiration, and photosynthesis of the widespread diatom-bearing LBF Operculina ammonoides were measured in laboratory experiments that included manipulation of carbonate chemistry parameters. pH was altered while keeping dissolved inorganic carbon (DIC) constant, and DIC was altered while keeping pH constant. The results show clear vulnerability of O. ammonoides to low pH and CO 3 2− under constant DIC conditions, and no increased photosynthesis or calcification under high DIC concentrations. Our results call into question previous hypotheses, suggesting that mechanisms such as the degree of cellular control on calcification site pH/DIC and/or enhanced symbiont photosynthesis in response to OA may render the hyaline (perforate and calcitic-radial) LBF to be less responsive to OA than porcelaneous LBF. In addition, manipulating DIC did not affect calcification when pH was close to present seawater levels in a model encompassing the total population size range. In contrast, larger individuals (>1,200 μm, >1 mg) were sensitive to changes in DIC, a phenomenon we attribute to their physiological requirement to concentrate large quantities of DIC for their calcification process. Plain Language Summary Large benthic foraminifera (LBF) are unicellular marine organisms that build calcium carbonate shells and live in association with oxygen-producing photosymbiotic algae. They are a significant component of tropical and subtropical marine ecosystems and play an important role in the chemical and biological balance of the oceans. Studies investigating the response of these organisms to ocean acidification are essential for understanding the impact of future ocean acidification on shallow subtropical costal systems. In this study, growth rates and oxygen production of a widespread LBF species were measured in laboratory experiments that manipulated key carbonate chemistry parameters. The results show clear vulnerability of this species to lower pH, regardless of the levels of dissolved inorganic carbon (which is the sum of all inorganic carbon in seawater). This finding calls into question recent suggestions that differences in the vulnerability of foraminiferal species relates to shell structure and type of symbionts. Rather, our results highlight that these factors do not necessarily offer protection against ocean acidification. Overall, this study contributes to our understanding of the impact of increasing carbon dioxide and ocean acidification on a key group...