Background and Objectives Implementation of automated steps in preparing blood components for transfusion from whole blood collections has produced improvements in multiple fields. The aim of this review is to summarize data from existing literature related to automation of whole blood processing systems. Materials and Methods We searched MEDLINE for studies comparing semi‐automated and fully automated whole blood processing systems published before 20 July 2021. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed. Additionally, we performed a manual search. Results We identified 500 studies, of which 459 (92%) did not meet the eligibility criteria, and finally 17 studies were included in the analysis. Manual search included six additional studies. Publication year ranged from 2004 to 2021. Automation reduced the run‐time (from 92 to 76 min), improved recovery of haemoglobin in red cell concentrates (RCCs) and resulted in higher red blood cell and platelet yields. Automation also reduced discard rates due to whole blood bag ruptures (1.2%–0.1%), low volume of RCCs (<200 ml; 0.5%–0.03%) and haemolytic plasma (2.1%–0.6%). Automation could reduce the number of full‐time equivalent (FTE) operators or maintain the number of FTE operators while performing additional procedures, and it reduced to 1.13 m2 the space required for the device. Conclusion Automation of whole blood processing resulted in continued improvements in productivity, product quality and technical features. However, too few publications are available to reach strong conclusions. Therefore, it is necessary to expand the scientific knowledge in this field.