Two teams battling adversity will meet in the March Madness Sweet Sixteen when Iowa State (29-7) and Tennessee (24-11) go head-to-head in Chicago.

Despite losing Joshua Jefferson three minutes into the NCAA Tournament, Iowa State has looked every bit like a No. 2 seed with a pair of dominant wins over Tennessee State and Kentucky. The Cyclones have received a lift from guards Tamin Lipsey and Killyan Toure in Jefferson's absence to advance to their third Sweet Sixteen in the last four years.

Tennessee also cruised in round one, ending the miracle season of Miami (OH), before squeezing past Virginia in the Round of 32. Star guard Ja'Kobi Gillespie has shouldered the load for the Volunteers in the tournament, averaging 25.0 points per game while Nate Ament nurses a hurt ankle.

March Madness odds courtesy of DraftKings Sportsbook.

Tennessee vs. Iowa State odds

Tennessee: +4.5 (-115)

Iowa State: -4.5 (-105)

Over: 139.5 (-108)

Under: 139.5 (-112)

Tennessee vs. Iowa State key injuries

Iowa State has dealt with arguably the most impactful injury of the 2026 NCAA Tournament when Joshua Jefferson hurt his ankle three minutes into the Round of 64. Jefferson missed the Cyclones' ensuing game against Kentucky and is considered a game-time decision against Tennessee.

Even if he plays, Jefferson will almost certainly be compromised just one week after sustaining a severe ankle sprain. Monitor his status during warm-ups, but Jefferson will likely not be at 100 percent either way.

Tennessee does not have any key players listed on its injury report, but star forward Nate Ament has not been at 100 percent since late in the regular season. Head coach Rick Barnes already admitted that Ament will play compromised for the remainder of the year.

Since hurting his leg against Alabama on Feb. 28, Ament has only averaged 11.4 points in his last five games.

Tennessee vs. Iowa State betting trends

  • Iowa State is 22-13-1 against the spread
  • Iowa State is 2-0 against the spread in March Madness
  • Iowa State is 7-6 against the spread as single-digit favorite
  • Iowa State is 16-20 to the over
  • Tennessee is 16-18-1 against the spread
  • Tennessee is 2-0 against the spread in March Madness
  • Tennessee is 3-1 against the spread as single-digit underdog
  • Tennessee is 17-18 to the over

Tennessee vs. Iowa State matchup

Iowa State and Tennessee are two similar programs, each dealing with injuries to their star player. The injuries to Joshua Jefferson and Nate Ament have subsequently shifted each team's approach.

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Iowa State and Tennessee have played through Jefferson and Ament in the paint all season. The Volunteers average the 19th-most points in the paint, with the Cyclones close behind at 32nd.

Likewise, each team is adept at defending the paint. Iowa State only allows 26.7 points in the paint, 27th-fewest in the country, while Tennessee only allows 26.1, ranking 19th.

However, Jefferson's absence and Ament's injury have convinced both teams to adopt a more perimeter-oriented attack. Iowa State has been playing through Tamin Lipsey and Killyan Toure to set up Milan Momcilovic on the perimeter, while Tennessee has handed the keys to Ja'Kobi Gillespie. Lipsey, Toure and Gillespie have been three of the best guards in March Madness.

Gillespie, in particular, has taken over, accounting for 32 percent of Tennessee's total points through its first two games.

As good as Iowa State and Tennessee are defensively, both are beatable from the outside, giving each the opportunity to hurt the other from deep. The Cyclones are averaging 10.0 triples while shooting 38.4 percent from deep through their first two games, with the Volunteers hitting 8.5 three-pointers on a 34.6 percent clip.

Tennessee vs. Iowa State prediction and pick

While Tennessee and Iowa State share many similarities, the Cyclones are a deeper, more well-rounded team, even if Joshua Jefferson remains sidelined. With a compromised Nate Ament, Rick Barnes' offense has boiled down to a heavy dose of Ja'Kobi Gillespie, who faces his toughest test of the season.

After winning a duel with Virginia's aggressive defense, Gillespie now faces an even better Iowa State perimeter defense, led by a pair of elite defenders in Tamin Lipsey and Killyan Toure. Lipsey has earned all the accolades as a three-time All-Big 12 defensive team member, but Toure's length and hand speed have given opponents the most issues all season.

With Gillespie facing an aggressive defender all game, Tennessee does not have much offense elsewhere. Gillespie has either scored or assisted on 32 of the Volunteers' 57 made field goals during their March Madness run. He is also their only consistent three-point shooter, making nine of their last 17 triples.

Conversely, Iowa State has been running through Lipsey, but the floor spacing and shooting have remained elite sans Jefferson. Tennessee will have to figure out how to stop the best shooter in the country, Milan Momcilovic, who hits an absurd 49.3 percent of his 7.6 three-point attempts per game.

Nate Heise and Jamarion Bateman have also stepped up for Iowa State in its last two games, along with Toure, who has suddenly doubled his offensive aggression.

Barring a truly legendary night from Gillespie, Iowa State is the more diverse team in its current state and a notch better on both ends of the court.

Final Tennessee-Iowa State Prediction & Pick: Iowa State (-4.5), Over 139.5 (-108)