Marco Benassi fired home from Fiorentina's first opening of the game to give the visitors the lead - an advantage they would defend diligently for the remainder of the game.
Another goal from Giovanni Simeone, just minutes before the break, gave Stefano Pioli's side control - and, despite carving out numerous opportunities, the Giallorossi were unable to get back into the game.
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Di Francesco made five changes from the side that lost in Barcelona, with Radja Nainggolan returning to the starting line-up as captain after missing the Camp Nou game through injury.
Elsewhere, Maxime Gonalons, Juan Jesus, Gregoire Defrel and Stephan El Shaarawy all came into the side.
6' - Goal. Fiorentina take an early lead. Benassi slots home from inside the box. 0-1.
10' - Strootman stings the palms of Sportiello with a swerving drive from the edge of the box.
10' - Manolas, under pressure, heads narrowly wide at the far post. Better from Roma.
13' - NO! POST! Sportiello fails to collect a looping ball; Dzeko reacts instinctively but his first-time shot from a tight angle hits the woodwork and goes wide!
15' - El Shaarawy chests the ball down and half-volleys at goal, but it's comfortable for Sportiello.
27' - CHANCE! Dzeko does brilliantly to outmuscle Vitor Hugo and get into the box, but Sportiello does well to charge down the striker's effort!
39' - Goal. Fiorentina double their advantage. Simeone breaks clear on the counter and fires home from inside the box. 0-2.
44' - Dzeko wins a free-kick in a dangerous position. The ball is rolled short to Radja but his typically powerful strike is charged down by the wall.
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46' - Immediate chance! Dzeko meets the low cross in from the left, but Sportiello makes a brilliant save low to his right to keep it out!
53' - Glorious opening again forthe Giallorossi; El Shaarawy clips the ball into the box for Dzeko, but the striker prods a first-time shot over the bar.
55' - Great chance! Roma slice Fiorentina apart with an incisive move forward: Schick feeds Radja inside the box but Sportiello blocks the shot!
70' - Another good chance... Dzeko flicks a header fractionally wide of the far post after a perfect ball in from El Shaarawy.
74' - BAR! Florenzi's cross is met by Schick - his glancing header beats Sportiello but crashes away off the underside of the crossbar!
90' - El Shaarawy fires wide under pressure.
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“It did not go well: when you create so much, and then concede two goals from three shots, then clearly the fault is ours. We defended badly. We’re in a tough spell, but today none of the key moments went our way.”
- Eusebio Di Francesco
Roma have two more games at the Stadio Olimpico to come, starting with the second leg of their Champions League quarter-final against Barcelona on Tuesday night.
On Sunday they are then back in action in the derby - the Giallorossi the nominal 'visitors' as they play Lazio in a hugely important game both at the top of Serie A and for city pride.
Goalscorers: Benassi (7'), Simeone (39')
Roma: Alisson; Peres, Manolas (Kolarov), Fazio, J. Jesus; Nainggolan, Gonalons, Strootman (Florenzi); Defrel (Schick), Dzeko, El Shaarawy.
Fiorentina: Sportiello; Laurini, Pezzella, Hugo, Biraghi, Veretout, Dabo, Benassi, Eysseric, Saponara, Simeone.
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