Hydrophobic organic contaminants (HOCs) affect phytoplankton at cellular to population levels, ultimately impacting communities and ecosystems. Baseline toxicants, such as some HOCs, predominantly partition to biological membranes and storage lipids. Predicting their toxic effects on phytoplankton populations therefore requires consideration beyond cell uptake and diffusion. Functional traits like lipid content and profile can offer insights into the diverse responses of phytoplankton populations exposed to HOCs. Our study investigated the vulnerability of five phytoplankton species populations to varying chemical activities of a mixture of polycyclic aromatic hydrocarbons (PAHs). Population vulnerability was assessed based on intrinsic sensitivities (toxicokinetic and toxicodynamic), and demography. Despite similar chemical activities in biota within the exposed algae, effects varied significantly. According to the chemical activity causing 50% of the growth inhibition (Ea50), we found that the diatom Phaeodactylum tricornutum (Ea50 = 0.203) was the least affected by the chemical exposure and was also a species with low lipid content. In contrast, Prymnesium parvum (Ea50 = 0.072) and Rhodomonas salina (Ea50 = 0.08), both with high lipid content and high diversity of fatty acids in non-exposed samples, were more vulnerable to the chemical mixture. Moreover, the species P. parvum, P. tricornutum, and Nannochloris sp., displayed increased lipid production, evidenced as 5-10% increase in lipid fluorescence, after exposure to the chemical mixture. This lipid increase has the potential to alter the intrinsic sensitivity of the populations because storage lipids facilitate membrane repair, reconstitution and may, in the short-term, dilute contaminants within cells. Our study integrated principles of thermodynamics through the assessment of membrane saturation (i.e. chemical activity), and a lipid trait-based assessment to elucidate the differences in population vulnerability among phytoplankton species exposed to HOC mixtures.