Cylinder deactivation is a well-known measure for reducing fuel consumption, especially when applied to gasoline engines. Mostly, such systems are designed to deactivate half of the number of cylinders of the engine. In this study, a new concept is investigated for deactivating only one out of four cylinders of a commercial vehicle diesel engine (“3/4-cylinder concept”). For this purpose, cylinders 2–4 of the engine are operated in “real” 3-cylinder mode, thus with the firing order and ignition distance of a regular 3-cylinder engine, while the first cylinder is only activated near full load, running in parallel to the fourth cylinder. This concept was integrated into a test engine and evaluated on an engine test bench. As the investigations revealed significant improvements for the low-to-medium load region as well as disadvantages for high load, an extensive numerical analysis was carried out based on the experimental results. This included both 1D simulation runs and a detailed cylinder-specific efficiency loss analysis. Based on the results of this analysis, further steps for optimizing the concept were derived and studied by numerical calculations. As a result, it can be concluded that the 3/4-cylinder concept may provide significant improvements of real-world fuel economy when integrated as a drive unit into a tractor.