Ocean acidification (OA) due to increased anthropogenic CO₂ emissions is affecting marine ecosystems at an unprecedented rate altering biogeochemical cycles. Direct empirical studies on natural communities are required to analyse the interactive effects of multiple stressors while spanning multiple trophic levels. We investigated the interactive effects of changes in CO₂ and iron availability on functional plankton groups. We used mesocosms manipulating the carbonate system from the start to achieve present (LC) and predicted future pCO₂ levels (HC). To manipulate dissolved iron (dFe), half of the mesocosms were amended with 70 nM (final concentration) of the siderophore desferoxamine B (DFB) on day 7 (+DFB and –DFB treatments). Manipulation of both CO₂ and DFB increased dFe compared to the control. During the 22 experimental days, the plankton community structure showed two distinct phases. In phase 1 (days 1-10), only bacterioplankton abundances increased at elevated pCO₂. In contrast, a strong community response was evident in phase 2 (days 11-22) due to DFB addition. The coccolithophore Emiliania huxleyi biomass increased massively at LC+DFB. HC negatively affected E. huxleyi and Synechococcus and high dFe (+DFB) had a positive effect in both. The rest of the plankton community was unaffected by the treatments. Increased dFe partially mitigated the negative effect of HC imposed on the coccolithophores, indicating that E. huxleyi was able to acclimate better to OA. This physiological Fe-mediated acclimation can diminish the deleterious effects of OA on carbon export and the rain ratio, thus affecting food web dynamics and future ecosystem functioning.