Cyanobacterial blooms are intensifying worldwide due to eutrophication and climate change, increasing cyanotoxin exposure to aquatic organisms. This study investigated the physiological, biochemical, and behavioural impacts of cyanobacterial blooms on the three-spined stickleback (Gasterosteus aculeatus), a widespread mesopredatory fish. Adult sticklebacks were exposed for two weeks to naturally collected bloom material dominated by toxic Nodularia spumigena, non-toxic Aphanizomenon sp., or a 50:50 mix. We measured toxin accumulation (NOD_eq), hepatic enzymatic activities (ethoxyresorufin-O-deethylase [EROD], glutathione S-transferases [GSTs], glutathione reductase [GR], and catalase [CAT]), and escape swimming performance (centre-of-mass velocity, angular velocity, distance, and duration) in a multiparametric endpoints approach. Sub-lethal toxin levels in muscle tissue ranged from 0.006 to 0.077 µg g⁻¹ d.w. Results showed that fish exposed to toxic-dominated treatments showed significantly elevated EROD activity (up to 200 % increase), moderate increases in GR and GSTs, and reduced CAT activity compared to controls. Notably, distance travelled during escape responses was reduced by ∼50 % in the high-toxicity treatment and showed an inverse correlation with EROD activity, suggesting a trade-off between detoxification effort and swimming performance. Overall, our results demonstrate that EROD is a sensitive biomarker for cyanotoxin exposure in fish under natural bloom conditions. This finding highlights the need to consider natural cyanotoxin effects when interpreting environmental assessments, particularly given the projected increase in bloom frequency and severity under future climate scenarios.