The detrimental effects of pollutants can be determined by measuring specific responses to pollutants - biomarkers. I had measured activity of the enzyme acetycholinesterase (response to organophosphorous and carbamate pesticides) and concentrations of metallothioneins (response to pollution with heavy metals) in Mediterranean mussels, collected at four sampling sites. Condition and gonadosomatic index were calculated in Mediterranean mussels and abiotic parameters of sea water (temperature, oxygen concentration, salinity and pH) were measured. Measurements were done in spring and autumn periods during year 2011 in order to find out if values of measured biomarkers were different between seasons and sampling sites. Selected sampling sites were: mussel farms at Debeli rtič (sampling site 00DB), marina Koper (sampling site 00TM) and mussel farms in Bay of Strunjan (sampling site 0024) and in Bay of Piran (sampling site 0035). Highiest activity of acetycholinesterase (AChE) was measured in the Mediterranean mussels from Bay of Strunjan (119 ± 18 μmol min-1 mg-1 in spring and 114 ± 6 μmol min-1 mg-1 in autumn) and in mussels from mussel farm Debeli rtič (118 ± 11 μmol min-1 mg-1 in spring and 109 ± 11 μmol min-1 mg-1 in autumn). The lowest AChE activity in both seasons were measured from mussels at sampling site 00TM in Bay of Koper: 75 ± 6 μmol min-1 mg-1 in spring and 60 ± 7 μmol min-1 mg-1 in autumn. Measured activity AChE from sampling site 0035 in Bay of Piran was 97 ± 12 μmol min-1 mg-1 in spring and 86 ± 8 μmol min-1 mg-1 in autumn. The highiest concentrations of metalothioneins (MT) were measured in autumn sampling in mussels from Bay of Piran: 79 ± 9 µg MT g-1 wet mass. The lowest values of MT were measured during autumn sampling (50 ± 6 µg µg MT g-1 wet mass) in mussels from Bay of Koper (sampling site 00TM). During autumn period concentrations of MT among sampling sites were more equal: at sampling site 00TM 60 ± 3 µg µg MT g-1 wet mass, similarly at sampling site 0035 in Bay of Piran (60 ± 10 µg µg MT g-1 wet mass) and 65 ± 9 µg µg MT g-1 wet mass at sampling site 00DB at Debeli rtič and 68 ± 10 µg µg MT g-1 wet mass in samples from sampling site 0024 in Bay of Strunjan. Significantly lower concentration of MT was measured at sampling site 00TM in Bay of Koper in autumn. No differencies between seasons were found. No seasonal changes between sampling sites were found in activity of AChE. I found out that the activity AChE in mussels from sampling site 00TM in Bay of Koper and in mussels from Bay of Piran (sampling site 0035) was significantly lower in both seasons, which points out chronic exposure to higher concentrations of pollutants which inhibit AChE in comparison with others sampling sites.