Messi and Co. are odds-on in the outright market but there could be a great bet in the relegation market with one of last season's promoted sides
While Real Madrid have dominated European football over the last five years, domestically it has been their eternal rivals Barcelona who have been the team to beat.
The Catalans have ended as champions of La Liga in seven of the last ten seasons and Ernesto Valverde's men are firm favourites to retain their crown.
Barca, as ever, will face competition from Real Madrid, while this season hopes are high for an Atletico Madrid side that have spent considerably in the summer transfer window.
Barcelona are priced at 4/6 (1.66) with bet365 to win the title once more, while Real Madrid can be backed at 15/8 (2.88).
The price for Atletico meanwhile has come in considerably with Diego Simeone's men offered at 15/2 (8.50).
There is then a massive jump in the market to Valencia at 100/1 (101.00) and Sevilla at 150/1 (151.00).
Beating their cross-city rivals in the UEFA Super Cup gave an indication that Atletico must be taken seriously this season and Simeone's side look better equipped for a title push than when they were actually crowned champions in 2014.
Of course it is always a big ask to finish above both Barcelona and Real Madrid, and Atleti are priced at 4/11 (1.36) to top the table without the big two.
Real Madrid have a new manager in charge and have sold their all-time leading goalscorer, while last season Barca were a little too reliant on Lionel Messi, so the 15/2 (8.50) price could certainly offer some value.
At the other end of the table, there are a number of teams who will be content with simply surviving.
Tiny Huesca are making their debut in the Spanish top flight and are the odds-on favourties to go straight back down at 8/13 (1.61) , whilst Valladolid also look likely to struggle at 6/4 (2.50).
It is Girona, though, that could offer some value to be relegated at 9/2 (5.50) as they enter their second ever season in the top flight.
Despite impressing in their debut campaign last term, a number of players who have returned to their parent clubs following loan spells and that could have an adverse effect.
Pablo Machin's ideas and energy have taken him to Sevilla and Girona are likely to miss his tactical expertise, meaning new man at the helm Eusebio Sacristan has a job on his hands to keep the Catalans up.
Prices correct at the time of writing. Please gamble responsibly.