Cook was carted off the field in the third quarter after being hit hard with his leg bent in an awkward position.
"One of my favorite guys broke his leg," Harbaugh said of Cook, who joined the Ravens late last season with after being cut by the New York Jets. "He's had a really good camp, and he's one of our most valuable special teams guys from last year. So, that was tough. I think it's in the lower leg, so it's a season-ending deal."
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Reserve safety Sean Considine sustained a more serious concussion after sustaining a minor one last week.
"This one we will have to look at really hard," Harbaugh said.
Later in the third quarter, nickel back and Pro Bowl special-teams ace Corey Graham was helped off the field by trainers.
Graham appeared woozy and was taken into the training room for concussion testing, but it was diagnosed as a stinger.