'RBC' is an initialism formed in medical English from the phrase 'red blood cell'; 'RBCs' is simply the plural form used in clinical and laboratory contexts.

The phrase 'red blood cell' developed from the words 'red' + 'blood' + 'cell'. Earlier scientific terminology included 'red corpuscle' (from Latin 'corpuscle' < 'corpusculum' meaning 'little body'). The scientific term 'erythrocyte' comes from Greek 'erythros' meaning 'red' and 'kytos' meaning 'container' or 'cell'. Over the 19th and 20th centuries the common English phrase 'red blood cell' became standard, and the abbreviation 'RBC' arose in clinical writing.

Initially described as 'red corpuscles' or 'erythrocytes' in early microscopy, the basic sense—cells in the blood that appear red and carry oxygen—has remained consistent; the modern abbreviation 'RBC(s)' simply shortens the established phrase.