Natural gas (NG), mainly composed of methane, is extremely resistant to autoignition. High efficiency premixed compression ignition (CI) combustion modes are therefore difficult to achieve in NG engines. One potential method for expanding the range of compression ignition operation in NG engines is to pretreat the fuel such that it becomes more reactive. This paper presents results from one-dimensional simulations of a medium duty multi-cylinder natural gas engine partially fueled by products from oxidative coupling of methane (OCM), a catalytic process by which methane is converted to C2 hydrocarbons like ethane and ethylene. First, the results of OCM reactor three-dimensional CFD simulations are presented to define the resulting product species distribution over a range of residence time. Using the reactor results, a one-dimensional model of an engine is implemented with and without OCM products to illustrate efficiency gains possible by operating in a compression ignition mode. Results of the modeling show that brake thermal efficiency improves by 1 to 7% with OCM-enabled CI combustion compared to spark ignition combustion of natural gas alone. The results also show that since the OCM reactor is exothermic, part of the incoming natural gas heating value is converted to sensible enthalpy. The OCM products therefore must be used to preheat the intake charge, thus avoiding an overall brake thermal efficiency (BTE) penalty. Overall, this study finds that OCM products have the potential to increase BTE of NG engines by allowing them to operate in premixed CI modes. Future work must look to improve OCM catalyst durability and reactor turndown ratio to provide a reliable high reactivity fuel stream for NG engines.