Coastal ecosystems, especially in rapidly industrializing regions, are increasingly threatened by pollution, necessitating the establishment of Marine Protected Areas (MPAs) to mitigate such impacts. In the environmentally challenged Northwestern Arabian Gulf (NWAG), the establishment of Sulaibikhat MPA in 2012 represents a critical step toward preserving vulnerable marine habitats. This study provides the first comprehensive evaluation of pollution stress in this MPA, focusing on microbial indicators, total petroleum hydrocarbons (TPH), polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and surfactants in seawater and sediment samples collected from October 2018 to March 2021. Microbial indicators, including total coliforms and Escherichia coli, were within acceptable limits, but sediment contamination with TPH (18.8 to 1339.7 ppm) far exceeded moderate pollution thresholds. PAH levels were low in seawater but elevated in sediments, revealing both pyrogenic and fresh petroleum contamination. Surfactant concentrations, particularly non-ionic types, exceeded toxicity thresholds for aquatic organisms, signaling significant ecological risk. Trace levels of banned persistent organic pollutants such as Endosulfan II and PCB 74, were detected after June 2019, suggesting ongoing pollution from agricultural and industrial sources. This study highlights the urgent need for targeted pollution control and sustainable management practices to preserve the ecological integrity of the NWAG MPA. The results serve as a baseline for future monitoring and policy formulation, crucial for safeguarding this key marine ecosystem in a region facing escalating environmental challenges.