Objectives: This study was conducted to examine the relationship between crude oil exposure and physical symptoms among residents participating in clean-up work associated with the Hebei Spirit oil spill, 2007 in Korea. Methods: A total of 288 residents responded to a questionnaire regarding subjective physical symptoms, sociodemographic characteristics and clean-up activities that occurred between two and eight weeks after the accident. Additionally, the urine of 154 of the respondents was analyzed for metabolites of volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) and heavy metals. To compare the urinary levels of exposure biomarkers, the urine of 39 inland residents who were not directly exposed to the oil spill were analyzed. Results: Residents exposed to oil remnants through clean-up work showed associations between physical symptoms and the exposure levels defined in various ways, including days of work, degree of skin contamination, and levels of some urinary exposure biomarkers of VOCs, metabolites and metals, although no major abnormalities in urinary exposure biomarkers were observed. Conclusions: This study provides evidence of a relationship between crude oil exposure and acute human health effects and suggests the need for follow-up to evaluate the exposure status and long-term health effects of clean-up participants.