To study the influence of environmental and biological factors on levels of contamination by Escherichia coli, Salmonella spp., hepatitis A virus (HAV) and norovirus in clam production areas, an epidemiological study was conducted on 791 samples of live clams (Ruditapes decussatus), 539 of which were sent for bacteriological analysis and 252 for detection of norovirus and HAV. These samples were collected in different production areas in the Sfax region of southern Tunisia over four consecutive years, from March 2013 to December 2016. The prevalence of positive samples was 36% for E. coli, 11% for Salmonella spp., 19% for norovirus and 3% for HAV. There was a significant correlation between contamination by E. coli and by Salmonella spp., as well as between contamination by noroviruses and by HAV and between contamination by noroviruses and by Salmonella spp. Temperature, the presence of migratory birds and tourism are the main factors affecting microbial contamination levels in bivalve molluscs.