The 2019-20 campaign is only 10 games old for the Spanish giants, but already both clubs have been blighted by injuries to many of their best players.
Barca have been without Lionel Messi, Luis Suarez, Ousmane Dembele, Samuel Umtiti, Jordi Alba, Junior Firpo, Ansu Fati and Neto for differing lengths of time this term, causing a selection headache for coach Ernesto Valverde – especially in attack.
And in Madrid, Real boss Zinedine Zidane has had even more players out, with Marco Asensio, Eden Hazard, Luka Modric, Isco, James Rodriguez, Luka Jovic, Marcelo, Fede Valverde, Brahim Diaz, Rodrygo, Thibaut Courtois, Ferland Mendy and Nacho all sidelined at various points between pre-season and early October. Some of them more than once. And now, Gareth Bale and Modric have picked up knocks on international duty.
Over the summer, Barca travelled to Japan for two matches, returned to the Catalan capital for their annual Gamper Trophy game, then flew to Miami and Michigan for back-to-back fixtures against Napoli.
An injury to Messi on his first day back in training saw the Argentine miss that trip and also the start of the season. He had returned late after appearing at the Copa America in June and early July and has not had a proper pre-season. Suarez also featured in South America's continental competition and was injured on the opening day of the campaign – a 1-0 loss at Athletic Club.
"Pre-season hasn't helped," Gerard Pique said at the end of September. "I think it's the year in which we have had the most trips and the least training sessions. And we are feeling it."
Coach Ernesto Valverde was asked at the same time if poor physical preparation was to blame and said: "I never give too much importance to the physical preparation. A lot of people do, but it's an ethereal way to influence the team, positively or negatively. In football, with so many games so close together, you prepare as you can."
And he added: "My team is in good shape. It's true we are having some setbacks, but I won't blame our pre-season. This is Futbol Club Barcelona and we know the commitments we have."
Messi also refused to blame the hectic pre-season schedule for Barca's injury problems in a recent interview, saying he 'understands' the need for money-making fixtures in the United States and Asia.
The five-time Ballon d'Or winner is still suspended following his controversial comments about the officials in the Copa America, so he missed the recent international break with Argentina and that will have been a relief to his club after his injury problems at the start of this season.
In August, both Dembele and Suarez went away after suffering injuries, the former having told the club he had not realised there was any problem as he travelled for a weekend in France and the latter pictured in Morocco with a heavily-strapped leg after the loss in Bilbao.
Both are back now, although the French forward will miss the Clasico due to his red card in the 4-0 win over Sevilla prior to the international break.
Toni Kroos, like Messi, missed the recent international between Germany and Argentina after he picked up a groin injury in Madrid's 4-2 win over Granada on October 5.
That means the midfielder was at least able to rest and recover instead of accumulating more games and journeys and he should be refreshed ahead of another busy period of fixtures starting away to Mallorca on Saturday.
"We have had seven games in 21 days following an international break and now there will be another," Zidane said when he was asked about his side's injury crisis ahead of their 2-2 draw at home to Club Brugge on October 1.
"The players are not machines and some of them never stop. A modern-day footballer, and even more so at Madrid, has to play every three days. You have no time to rest. I used to play 45 games and now they play 60... almost two seasons in one."
Madrid, like Barca, were busy in pre-season – even more so in fact. Los Blancos travelled to the United States for fixtures in Houston, Landover and East Rutherford, before two games in Munich, one in Salzburg and another in Rome.
Hazard was then injured on the eve of Madrid's La Liga opener away to Celta Vigo and Zidane has had just three midfielders to choose from at times in an injury-hit start to the campaign. Now, the French coach will be sweating on the fitness of both Bale and Modric after the two former Spurs players picked up knocks on international duty this week.
But while some have been quick to point the finger at Real Madrid's fitness trainer Gregory Dupont, the reality is that Los Blancos suffered just as many injuries last term when the popular Antonio Pintus was in charge.
The teams' hectic pre-season schedules, on top of summer tournaments with national teams, international breaks during the season, plus league, cup, Champions League, Supercopa fixtures and so on means there is no respite for the world's top players.
Interest from fans and audiences around the world in seeing the finest footballers as much as possible brings money to clubs' coffers from promoters, sponsors and television companies, yet it comes at a price.
Both Barca and Madrid have had their start to the season disrupted and after this international break is out of the way, the two teams will have eight games in the space of three weeks – six apiece in La Liga and two in the Champions League.
Another international break then follows in November, before seven more games in a month and then a winter break which will at last allow the two teams to rest, although a four-team Spanish Supercopa series is planned for January in Saudi Arabia and the Copa del Rey also gets under way in the same month.
It never stops and, while this rapid rate of games continues, the injuries are unlikely to either.