The Chelsea boss confirmed Cole would miss the Champions League clash at Stamford Bridge as a result of a hamstring injury picked up during the 1-1 draw at Swansea on Saturday.
“It’s a real shame because he’s got all the experience that you need in games like this,” said Di Matteo.
“It’s a real blow for us. Unfortunately, during a long season and with all these games you play, you have to take into consideration that you might have a few injuries.
“Ryan has always performed very well for us every time he played. He’s got a little bit of experience [now] which helps and I’ve every confidence that he’s going to play a great game.”
Di Matteo, whose side are currently three points behind Group E leaders Shakhtar, knows nothing more than a victory will do at Stamford Bridge.
“We certainly have to win our home games now and hopefully we can do that tomorrow,” he said. “If we win it’s all in our hands and that’s what we want to do.
“Every individual needs to be able to perform at the highest peak of their ability.
“The early goal [in Donetsk last month] helped them massively because it allowed them to play a little bit on the counter instead of break us down.
“It’s important we start well, get the crowd behind us and draw confidence from a good start.
“We are a very strong team at home, we need to show that and put them under pressure.”
Di Matteo was also quizzed on his relationship with Chelsea owner Roman Abramovich at his pre-match news conference.
“I think we have a very good relationship; as good as it can be between a manager and an owner,” he said.
“We have good communication levels. He’s fully behind us and he likes to be supportive of the team. I fully feel the support from him and the confidence.”
• Chelsea won all three home group games in 2011-12, scoring ten goals without conceding, and recorded three more home victories in the knockout stages as they claimed the trophy for the first time.
• Fernandinho and Willian play with Luiz, Ramires and Oscar in the Brazilian national team.
• Alex Teixeira’s goal on matchday three was the 100th Chelsea have conceded in the Champions League, group stage to final.
• Chelsea’s 4-0 victory at Nordsjælland on matchday two was the fifth time the Blues have scored four or more goals in an away Champions League game.
MORE: Man United latest news
MORE: Arsenal latest news
MORE: Chelsea latest news
MORE: Liverpool latest news