Diesel engine cylinder deactivation (CDA) can be used to reduce petroleum consumption and greenhouse gas (GHG) emissions of the global freight transportation system. Heavy duty trucks require complex exhaust aftertreatment (A/T) in order to meet stringent emission regulations. Efficient reduction of engine-out emissions require a certain A/T system temperature range, which is achieved by thermal management via control of engine exhaust flow and temperature. Fuel efficient thermal management is a significant challenge, particularly during cold start, extended idle, urban driving, and vehicle operation in cold ambient conditions. CDA results in airflow reductions at low loads. Airflow reductions generally result in higher exhaust gas temperatures and lower exhaust flow rates, which are beneficial for maintaining already elevated component temperatures. Airflow reductions also reduce pumping work, which improves fuel efficiency. The fuel economy and thermal management benefits of one-third engine CDA, half-engine CDA and two-third engine CDA have been studied at key operating conditions. CDA improves the fuel efficiency at steady state loaded idle operation by 40% with similar engine out temperatures and lower exhaust flow rates compared to conventional thermal management strategies as demonstrated with an inline six (I6) cylinder medium duty diesel engine used in this study. The lower exhaust flow rates due to CDA help maintain elevated A/T temperatures via reduced heat transfer losses. At elevated engine speeds, CDA provides a 5% - 32% BTE improvement in fuel economy, increased rate of A/T warm-up, higher temperatures steady state temperatures, and allow for active diesel particulate filter regeneration without hydrocarbon dosing of the diesel oxidation catalyst. During highway cruise, half-engine CDA and two-third engine CDA can be used to reach engine outlet temperatures of 520 to 570° C, a 170 to 220° C increase compared to normal operation. Full engine CDA enables 78% reduction in motoring torque at an engine speed of 2100 rpm and thus could help save fuel and keep the A/T warm during vehicle coast.