The disease "traps" people in their own body, able to think, but incapable of moving or talking.
The study of 65 patients, published in the British Medical Journal's BMJ Open, found 72% reported being happy, with just 7% wanting help to commit suicide.
Experts said it showed it would be unwise to make assumptions about people's mental state.
The findings could also have implications on the assisted suicide debate, the researchers said.
However, they warned that there could be some bias in the study with the most unhappy patients refusing to take part.
The participants, from the French Association for Locked in Syndrome, responded by blinking or moving their eyes.Happy
About half of those questioned, 55%, had recovered some speech and 70% had recovered some limb movement.
The majority, 72%, said they were happy and 68% said they never had suicidal thoughts.
The longer people were locked-in, the more likely they were to be happy.
Researchers at the University of Liège, Belgium, said: "We suggest that patients recently struck by the syndrome should be informed that, given proper care, they have a considerable chance of regaining a happy life.
"In our view, shortening of life requests are valid only when the patients have been give a chance to attain a steady state of subjective wellbeing."
Dr Adrian Owen, from the Centre for the Brain and Mind at the University of Western Ontario, said: "This is an extremely important study with a clear message - we cannot, and should not, presume to know what it must be like to be in one of these conditions.
"I think most of us feel that life in a lifeless body would not be a life worth living, but this study demonstrates that this is not always the case.
"On the basis of the results, it would be unwise for us to make assumptions about the mental state of those individuals."
Locked in Syndrome
- Condition in which patient is mute and totally paralysed, except for eye movements, but remains conscious
- Usually results from massive haemorrhage or other damage, affecting upper part of brain stem, which destroys almost all motor function, but leaves the higher mental functions intac