Friendly Preview: Brazil v Portugal
Team doctor Henrique Jones confirmed that the Real Madrid star is struggling with tendonitis and will miss out following his hat-trick heroics in Portugal's 4-2 win over Northern Ireland on Friday in FIFA World Cup qualifying.
"He has had a week of intense treatment, he made an enormous sacrifice and now he needs to rest," Jones said.
Ronaldo's three goals helped Portugal recover from 2-1 down at Windsor Park, where they finished with 10 men after Helder Postiga was dismissed, and increased the 28-year-old's international tally to 43, overtaking the iconic Eusebio's 41 and putting him second only to Pauleta on 47 in the country's all-time scoring charts.
Victory over Northern Ireland, who finished with nine men, also put Portugal two points clear of Russia at the top of Group F as the road to the World Cup in Brazil next year continues.
Brazil boss Luiz Felipe Scolari, who had a five-year spell in charge of Portugal between 2003 and 2008, also has injury concerns, with defender Dani Alves (knee) and Hulk (thigh) set to miss the clash at the Gillette Stadium, which is home to NFL franchise the New England Patriots.
That could mean that Roma's Maicon is drafted in alongside David Luiz and Thiago Silva at the back, while Barcelona's big-money signing Neymar is set to spearhead his side's attacking threat.
The Confederations Cup winners have only lost one game so far this year, a surprise 1-0 defeat to Switzerland, and will be looking to build as much momentum as possible before playing host to the World Cup in 2014.
Portugal are undefeated in their last six international outings, but have only beaten Brazil four times during their 19 previous meetings, the most recent being a 2-0 friendly win in 2007 when Simao and Ricardo Carvalho scored in the last 10 minutes.