Phycotoxins (marine algal toxins) are toxic metabolites released by certain phytoplankton species. They can be responsible for seafood poisoning outbreaks because filter-feeding mollusks, such as mussels, can accumulate these toxins throughout the food chain and present a threat for consumers’ health. A wide range of symptoms, from digestive to nervous, are associated to human intoxication by biotoxins, characterizing different and specific syndromes, called shellfish poisoning. The aim of this study is to compare the seasonal and spatial phycotoxin profiles of mussels (wild and farmed) harvested from South Bulgarian coast in the period 2017-2018. Analyzed were 57 samples by different analytical techniques - liquid chromatography tandem mass spectrometry (LC-MS/MS) and high-performance liquid chromatography with fluorescent detection followed by postcolumn derivatization. Domoic acid (DA), yessotoxin (YTX), pectenotoxin-2, PTX-2sa/ epi-PTX-2sa and gonyautoxin-2 (GTX2) were detected in the studied samples. Results revealed huge seasonal variations in the phycotoxin profiles of the mussels investigated. Spring 2017 profile is dominated by domoic acid present in 67% of the samples and reaching highest level of 618.9 ng. g-1. In summer 2017 samples YTX is prevalent (60%) reaching a level of 8.3 ng.g-1. No phycotoxins were detected in samples from fall 2017. The epimer pair PTX-2sa/ epi-PTX-2sa was with highest seasonal abundance in winter-spring 2018 – 47%. Its maximum detected level was 7.1 ng.g-1. No statistically significant differences in mean phycotoxin levels of different sampling locations were determined. Generally, the herein reported marine toxins levels are comparable or even lower than in other European studies and much lower than legislative limits set in EU. Nevertheless, the huge seasonal variations in the phycotoxin profile show that for protection of consumers’ health a further surveillance on marine toxins content in edible mussels is required.