Coastal marine environments are one of the most productive ecosystems. Nevertheless, anthropogenic activities have a significant influence on coastal marine biodiversity, resulting in functional changes in the microbial communities. The presence of antibiotic-resistant bacteria in coastal marine water is a global public health threat. The current study aimed to investigate the antibiotic resistance profile of opportunistic pathogenic bacteria isolated from coastal marine water in Jazan (Saudi Arabia). Seven coagulase-negative Staphylococci of five species were identified as Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus equorum, and Staphylococcus epidermidis. Moreover, the Gram-negative isolates were identified as Providencia rettgeri, Providencia vermicola, and Pseudomonas oleovorans. Alarming levels of resistance were determined for the bacterial strains S. epidermidis MG13, S. haemolyticus MG14, and P. rettgeri MG7. The existence of multi-drug resistant opportunistic pathogenic bacteria in the coastal marine water in Jazan could pose a potential threat to human health.