Du Plessis showed promise as a rugby player early, being named as captain of the Eastern Free State age-group team at Craven Week in 1995.

He studied medicine at the University of the Free State[5] and worked as a doctor, making him one of the few players in the professional era of rugby union to have another career outside of the sport.

[6] After recovering, he was selected for the Springboks squad for the first time during the 2007 Tri Nations, making his debut in the starting XV on 7 July against Australia during the Boks' home leg.

When interviewed after his selection, he said that his first sleep since 29 September was "an hour or so on the plane from Bloemfontein to Cape Town", where he travelled to do his required paperwork before joining the Boks in France.

In the early morning hours of 29 March, Brumbies lock Shawn Mackay was hit by a car outside a Durban nightclub, suffering a paralysing injury.