Volatile organic chemical exposure resulting from surgical operations is common in operating room personnel. The potential risk of long-term exposure to these low-level chemicals is always a concern. This study was conducted in an area hospital located in northern Taiwan to investigate the internal exposure scenario for operating room personnel. Breath samples were collected before and after surgery, whereas area samples were collected during the surgeries in process. There were 18 volatile organic compounds identified in the samples with gas chromatography-mass spectrometry. The average concentrations of sevoflurane (P = 0.0082), dimethyl sulfide (P = 0.0550), and methyl methacrylate (P = 0.0606) in breath samples collected after surgical operations were significantly higher compared to those obtained before surgical operations, whereas only slight elevations were present for benzene and hexamethyldisiloxane (P < 0.100). In addition, electrosurgical smoke-related chemicals, such as benzene, toluene, ethylbenzene, and m/p-xylene, also presented higher levels in operating room samples compared to the control area. Specifically, the findings in this preliminary study suggested the associations of elevated exposure to sevoflurane across various surgeries to methyl methacrylate with orthopedic surgery and to hexamethyldisiloxane with conventional electrosurgical units. Future study is warranted to explore the short-term high-level chemical exposure in operating rooms and to propose effective preventive measures accordingly to keep any exposure to chemicals at the lowest practical level.