In the coastal areas of the world, most Vibrio species have been incriminated as notorious agents causing foodborne, wound and other infections. These pathogens are known to be associated with the consumption of raw or undercooked seafoods or the exposure of wounds to warm seawater. Aim: Therefore, this research work was designed with the aim of assessing the microbiological quality of the water bodies as well as the seafoods consumed in Cross River State (CRS). Study Design: The Study was designed using the completely randomized block design and the data was analyzed using of two-way analysis of variance, Generalized Linear Model Univariate analysis. Significant means were separated using the Least significant difference (LSD). Place and Duration of Study: This study was done in the Department of Microbiology, University of CRS, Calabar, CRS, Nigeria, between 2016-2019. Methodology: we evaluated a variety of seafoods viz; crayfish, blue crabs, Periwinkles, apple nails, red lobsters etc. collected from major Beaches, markets and other sale points and water sources (rivers streams sea and gutters) in Calabar, CRS of Nigeria, using standard bacteriological techniques, for the prevalence of Vibrio species. Results: The mean percentage mean viable cell counts obtained ranged from 1.79±3.45 (seawater)-9.15±4.79CFU/mL (gutter water) and 7.68±7.58 (Blue Crab)- 11.37±4.82 CFU/g (fish) in the Rainy season.  The counts for the Dry season Ranged from 1.79 ±3.42 (Seawater)-8.94± 4.51(gutter water), and 5.83 7.21 CFU/g (apple snail) -12.64 5.95 CFU/g (Fish). The total percentage mean counts obtained were 8.09±6.91 CFU/mL in the Rainy Season to 7.61±6.58 CFU/mL in the dry Season. From both seasons, the overall total mean count was 11.09±5.94 CFU/ml. From the nine locations evaluated in this study, it was observed that the Mean percentage counts for the Northern Senatorial District (NSD) ranged from 2.81± 3.49 (Ogoja)- 3.14 ±4.07CFU/mL (Obudu). For the Central (CSD) the range was from 3.34 ±4.20 (Boki)- 9.89 ±5.15 (Ikom), while for the Southern (SSD) it was from12.01± 6.52 (Akamkpa)- 14.47 ±5.44 (Calabar). The overall Total percentage mean counts from all the three Senatorial Districts was 14.03±4.86 CFU/mL. From the Northern Senatorial District, the total Percentage mean was 3.01±3.77 CFU/mL, 7.05±5.79 CFU/mL from the Central and 13.49± 5.72 CFU/mL from the Southern Senatorial District.  The Vibrio pathotypes isolated include Vibrio cholerae (V. cholerae) (both O1 and non-O1 serotypes) 1155 (31.61%), Vibrio parahaemolyticus (V. parahaemolyticus), 752 (20.58%), Vibrio fluvialis (V. fluvialis) 480 (13.14%), V. vulnificus 473 (12.94%) Vibrio mimicus (V. mimicus) 400 (10.95%) and Other Vibrios 394 (10.78%). Out of the 3654 Vibrio isolates, the greatest number 663±3.31 (18.14%) were from Seawater, while the least 133±.84 (3.64%) were from the Gutter Water. Also, the highest number 1245±2.61 (34.07%) came from Calabar, and the least 102±.65 (2.79%) from Obanlikwu. The NSD had the least number 327 (8.95%), followed by the CSD with 570 (15.59%) and then the SSD with 2757 (75.45%) as the highest number of isolates. Conclusion: The presence of these pathogenic bacterial species in common seafoods in this area is of great public health concern. It is therefore important that serious emphasis be laid on proper cooking of these seafoods as well as the establishment of regular hygiene surveillance strategies in the state.