A rapid combustion event occurred within the cab of a passenger vehicle while it was being driven down the interstate with four people inside, two each in the front and back. The person in the front-right seat was breathing gaseous oxygen from a small portable liquid oxygen (LOX) tank at a rate of 2 L/min, while a large portable LOX tank used to fill the small portable tank was stored inside the trunk. A flash fire immediately engulfed the occupant in the rear-right seat when she lit a cigarette, and it rapidly spread throughout the rest of the cab. This paper presents the forensic analysis of what caused the enrichment of oxygen (defined as 23 vol% or greater in this study) within the cab of the vehicle. Utilizing carbon monoxide as a tracer gas, the air exchange rate of a moving exemplar vehicle was measured under different ventilation conditions (no ventilation, high recirculation, and medium fresh air ventilation). The range of measured air exchange rates (air changes per hour, or ACH: 11–65 ACH), vehicle compartment volume, normal and maximum allowable evaporation rates of the small and large portable oxygen tanks, and typical exhalation rates of a person breathing pure oxygen were used as variables in a gas-mixing model to calculate the steady-state oxygen concentration within the cab of the vehicle. The results of the study showed that enrichment was not from the combination of the normal or maximum allowable evaporation rates of the tanks and the exhalation rate of the passenger breathing oxygen but from the enhanced venting of oxygen out of the large portable tank from component failure or outside influence on the tank, or both.