Nimoy revealed that he had been diagnosed with chronic obstructive pulmonary disease (COPD). On Twitter, he said: "I quit smoking 30 yrs ago. Not soon enough. I have COPD. Grandpa says, quit now!! LLAP (Live Long and Prosper)." On February 19, 2015, Nimoy was rushed to UCLA Medical Center for severe chest pains after a call to 911. According to accounts, he had been in and out of hospitals for the "past several months.

Nimoy died on February 27, 2015 in his Bel Air home from final complications of COPD, according to his wife Susan. He was 83 years old, and is survived by Susan and his two children and six grandchildren from his first marriage.

Zachary Quinto, who portrayed the younger "Spock" character in films Star Trek and Star Trek Into Darkness, commented on Nimoy's death: "my heart is broken. i love you profoundly my dear friend. and i will miss you everyday. may flights of angels sing thee to thy rest