The Portuguese forward says he is "unhappy" at the Bernabeu and has so far failed to reconcile the "professional issues" that led him to speak out.
Though Ronaldo is expected to start his 150th game for Real Madrid, the Spanish champions are beset by a sense of unease over their star player.
When allied to a poor run of early-season form that has seen them collect only four points from three games to already put them five points behind Barcelona, it is clear that Jose Mourinho requires a trouble-free trip to Seville.
He also needs Ronaldo to be on top form, as Opta's stats demonstrate just how key he is to Madrid's title hopes. Over the past three-and-a-bit seasons he has been involved in over 40 per cent of Madrid's Liga goals.
Since signing Ronaldo for £80 million in the summer of 2009, Real Madrid have also fared markedly worse when he is not in the team, seeing their win percentage slip from 81 to 69.
Meanwhile, Sevilla president Jose Maria Del Nido has been the most vocal critic of the stranglehold the big clubs exert over TV rights income and his side will be hoping to make a point on the pitch.
The lack of a collective bargaining system in La Liga means Real and Barcelona account for about half the TV pot of 600 million euros.
That helps make them the world's richest clubs by income, with annual earnings close to 500m euros, and means they can afford to buy the best players and pay the highest wages.
Del Nido has called La Liga "a load of rubbish", saying only the big two have a realistic chance of winning the title, and there is widespread support among other clubs for the introduction of a revenue sharing system like those used in rival European leagues.
However, Real and Barca have shown little sign they are prepared to cede to such demands as they look to protect their status as dominant powers.
Real, who dropped five points in their opening three games this season, have put 15 goals past Sevilla in their last three league meetings including a pair of crushing 6-2 victories in the Andalucian capital.
Under coach Michel, a former Real player, Sevilla are undefeated this term but in recent years have looked a shadow of the side that won consecutive UEFA Cups in 2006 and 2007 and are not even in European competition this season.
Del Nido issued a rallying call to Sevilla fans this week, urging them to get behind the players for the Madrid clash at the Sanchez Pizjuan, while Michel said on Thursday it was a chance for the team to kickstart their campaign.
"I would give my contract if that is what it takes to get a win against Real Madrid and that turned into the start of a positive run," Michel told Sevilla's TV channel.
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