Barcelona will have to continue their march at the top of La Liga without Tito Vilanova after it was revealed the coach has suffered a relapse of a tumour on which he was operated just over a year ago.
The 44-year-old who took over from Pep Guardiola at the beginning of the season was thought to have fully recovered from surgery last November to remove the growth on his parotid gland, and he was back at work within 15 days.
However after an operation on Thursday it is thought he will have treatment for at least six weeks and he may or may not be available to return to work at some stage during that time.
Until then, Sporting director Andoni Zubizarreta confirmed on Thursday, the side will be led by Vilanova's assistant Jordi Roura.
"Without going into too much detail about the sporting side today and whether we win or not at Valladolid on Saturday, just to say we'll continue with our coaching staff and our way of working, we'll be in extraordinary hands and Tito I'm sure will be watching us on TV," he said.
Barca president Sandro Rossell added "the most important thing for the club at this moment is the full recovery of Tito".
Vilanova has led Barcelona to the most successful start to a season in La Liga's history, with 15 wins and one draw in 16 matches so far.
With the final round of La Liga games of 2012 brought forward to allow the players an extra day of Christmas holidays, Barca will make it a great finish to the year, on the pitch at least, if they take three points at Valladolid.
Last weekend's win over closest rivals Atletico Madrid increased the Catalan side's lead to nine points and with Real Madrid's surprise draw with Espanyol leaving them 13 points back in third, for some La Liga title is already destined for the Nou Camp in May.
That win was followed with the news on Monday that Carles Puyol and Xavi Hernandez will stay at Barca until at least 2016 and Lionel Messi until 2018, and it was all looking positive until Wednesday's shock news.
Last Sunday's clear dominance over their closest rivals Atletico Madrid, especially in the second-half of the 4-1 win left most observers concluding that it is the Catalan side's title to lose.
Meanwhile Real Madrid face a tricky trip to fourth placed Malaga less than a week after manager Jose Mourinho said the title was "almost impossible now."
Defeats at Getafe, Sevilla and Betis, followed by the draw with Espanyol last Sunday, have left Madrid far adrift from table-toppers Barca.
One player the 'Merengues' missed last Sunday was French forward Karim Benzema.
Benzema is closer to a return than colleague Gonzalo Higuain, but could still miss the trip to Malaga with a foot injury. However he has plegded his future to the club this week, despite his name being linked with Paris Saint-Germain.
Malaga come into the game with the best defensive record in the league having conceded only 10 goals in 16 games and full-back Nacho Monreal is confident.
"We're going to be up for the Madrid match, we're doing well, we're at home and we know that Madrid is not going too good, but they're a good team and it will be difficult. I just hope we can take our chances and get the three points," he said.
In this week's maches already played, Rayo Vallecano beat Levante 3-0, Real Sociedad edged Sevilla 2-1 and Espanyol defeated Deportivo La Coruna 2-0, on Thursday.
On Friday, substitute Adrian Lopez hit an important winner as Atletico Madrid beat Celta Vigo 1-0.
Their win, Atletico's ninth straight victory at home this season, moves the club from the capital to within six points of Barca, in second position.
Earlier on Friday, Valencia beat Getafe 4-2 at home to make it two wins out of three for new manager Ernesto Valverde.
Betis v Mallorca (1500 GMT), Valladolid v Barcelona (1700 GMT) Osasuna v Granada (1900 GMT), Malaga v Real Madrid (1900 GMT) Athletic Bilbao v Zaragoza (2100 GMT)