Oysters are known for their nutritional value as a protein source in the human diet. The present study assessed the microbial quality of the oysters collected from Negombo Lagoon. Oysters and associated water samples were collected from four locations in the lagoon on a monthly basis from October 2021 to August 2022. The salinity, temperature, and pH of each location were also measured in situ. The samples were tested for aerobic plate count (APC), total coliforms, faecal coliforms and Escherichia coli (E. coli) following Sri Lankan Standards (SLS). Statistical analysis was performed using MINITAB 17. The results indicated that the APC in oysters (from 0 to 1.14 x 102 CFU/g) resulted in<5x105 CFU/g, the maximum recommended bacterial count for good quality seafood, while the water showed APC from 1.6 to 1.8 x 103 CFU/mL. The total coliforms and faecal coliform counts in oysters were from 2.67x10-2 to 166×10-2 MPN/g and from 6.67 x 10-2 to 93.3 x 10-2 MPN/g, while these counts in water samples were from13.3 to 366.7 MPN/100mL and from 4.30 to 194 MPN/100 mL respectively. E. coli levels in oysters varied from 1.00 to 81.0 x 10-2 MPN/g, which were below the maximum recommended level (11 MPN/g) for good quality seafood. E. coli levels in water ranged from 1.33 to 93.3 MPN/100 mL. The findings further revealed that the correlations between E.coli in water and water quality parameters were statistically insignificant and weakly positive. But, the correlation between E.coli in oysters and respective water showed a strong positive correlation and it was statistically significant (p<0.05). Although the oysters collected are suitable for direct consumption as per European shellfish harvesting area classification criteria, the microbial counts in water were higher than those of the oysters. Therefore, depuration of oysters is recommended for safe human consumption while continuous monitoring is conducted.