Horwill was all set to skipper the Reds against the Chiefs on the Sunshine Coast but an unrelated problem has forced him to pull out.
The 27-year-old rolled his ankle in training ahead of his side's final pre-season friendly and is now a doubt for the competition opener against the Brumbies in Canberra on February 16.
#TeamRehab wants me for a few days longer," Horwill tweeted.
"Extremely frustrated not being able to play this week. Just a tweak of the ankle
The setback happened in a full-contact session and, although scans have subsequently shown no major damage, Reds boss Ewen McKenzie isn't willing to take any risks with one of his star assets.
"There were six guys in the tackling drill but no one's owning up to doing it," said McKenzie wryly.
"James can't take a trick. It's disappointing he won't get some time in this game but it's just a tweak that delays his return a week.
"There's no dramas but he's obviously very disappointed about it, as we are, because he's put a lot of work into getting back on the field.
"I want to ensure he is 100 per cent. Obviously, it puts some doubt on him for the first game. That's what it is, but we want to make sure his comeback is 100 per cent successful."
Horwill hasn't featured for his franchise since his hamstring problems began in May but his absence from the Wallaby side dates back even further.
Having been appointed his country's captain in August 2011, Horwill hasn't worn the Green and Gold since the end of that year.
He missed the summer Tests with Scotland and Wales, the entire Rugby Championship campaign, the third Bledisloe Cup clash with New Zealand and the recent tour of Europe.