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Planktonic heterotrophic prokaryotes (HProks) are a pivotal functional group in marine ecosystems and are highly sensitive to environmental variability and climate change. This study aimed to investigate the short-term effects of increasing carbon dioxide (CO 2 ), ultraviolet radiation (UVR), and temperature on natural assemblages of HProks in the Ria Formosa coastal lagoon during winter. Two multi-stressor microcosm experiments were used to evaluate the isolated and combined effects of these environmental changes on HProk abundance, production, growth, and mortality rates. The isolated and combined effects of increased CO 2 on HProks were not significant. However, HProk production, cellular activity, instantaneous growth rate, and mortality rate were negatively influenced by elevated UVR and positively influenced by warming. Stronger effects were detected on HProk mortality in relation to specific growth rate, leading to higher HProk net growth rates and abundance under elevated UVR and lower values under warming conditions.