The departure of the Brazilian has left a sizeable gap in the Catalans' forward line and, while they still boast two of the world's best attacking players in Lionel Messi and Luis Suarez, the feared trident of MSN is no more.
Ernesto Valdverde will have to decide how to adapt the starting XI without Neymar and the new manager seems to have a couple of options. Either he brings in a forward like Paco Alcacer or Gerard Deulofeu and maintains a front three, or he changes things up and brings an extra body into midfield.
Real Madrid manager Zinedine Zidane has a similar dilemma with the suspension of Luka Modric, and the absence of the Croatian also potentially means a change in formation.
The Frenchman will either go for three up front in Ronaldo, Benzema and Bale or play with two of those and bring in the likes of Isco or Dani Ceballos into midfield.
Whichever formation the respective managers chose to deploy, this is a fixture which almost always produces goals and bet365 offer Messi as the lowest priced player to net at 8/11 (1.73). Just behind him in the betting is Cristiano Ronaldo at 19/20 (1.95), while Luis Suarez and Karim Benzema are offered at 21/20 (2.05) and 6/5 (2.20) respectively.
The man of the match in Real Madrid's victory over Manchester United in the UEFA Super Cup on Tuesday was Isco, with the Spain international scoring what proved to be the winner. The 25-year-old ended last season exceptionally and his showing against United points towards him picking up where he left off.
He can be backed at 13/5 (3.60) to score his first ever goal in a Clasico, and at 10/1 (11.00) to open the scoring. Meanwhile, Barcelona midfielder Ivan Rakitic is offered at the same odds as Isco and the Croatian scored a stunning strike in the last official meeting between these two sides in April.