Engine oil is considered one of the sources for pre-ignition in downsized boosted direct injection spark-ignited engines. When interacting with fuel sprayed in the combustion chamber, engine oil forms an ignitable mixture and can cause an ignition event before firing the spark plug. Because high research octane number (RON) fuels are difficult to auto-ignite and tend to suppress the knock in an internal combustion engine, studying their interaction with engine oil is essential. Hence, in the current study, a suitable lubricant oil surrogate, namely, n-hexadecane, is mixed with iso-octane and n-heptane at different concentrations to investigate the auto-ignition behavior at elevated pressures. Five sets of fuels (PRF0, PRF20, PRF50, PRF80, and PRF100) were prepared to get a wide range of RONs and blended with n-hexadecane at 15, 25, 35, and 45% mixture concentrations (vol %). These experiments were conducted in a constant volume combustion chamber, keeping the initial temperature constant at 300 °C. A single droplet of the mixture was suspended on a thermocouple bead to record the droplet’s lifetime temperature. It was observed that hexadecane mixed with PRF0, PRF20, PRF50, and PRF80 showed similar auto-ignition behaviors. The time of ignition (TI) for these mixtures initially increased until 25% concentration of the fuel in n-hexadecane, and further addition of fuels to 35% and higher concentrations showed a gradual decrease in TI. Ignition of mixtures with 35% and 45% fuel concentrations is attributed to n-heptane, as its low temperature chemistry is the dominant factor in its high reactivity compared to iso-octane. TI increased with the increasing concentration of PRF100 mixtures in hexadecane, unlike other PRF fuels tested in this study. This is because iso-octane is a high RON fuel with a higher auto-ignition temperature, making it challenging to auto-ignite.