In a video message, the Duke of Cambridge urged emergency service staff, care home employees and ambulance workers to “take care of yourself too”.
The message comes after Prince William and wife Kate promised to make campaigning on mental health their “top priority” in the coming months.
Prince William was speaking for the Our Frontline Initiative, supported by the prince’s charity foundation for emergency workers who may be suffering from mental health issues.
He said in a video posted on the Our Frontline Twitter account: “I want to say a huge thank you from myself and Catherine for all you are doing to keep everyone safe.
“You and your families are making huge sacrifices, and we want you to know that the whole country is enormously proud of you.
“The challenges you are facing, day in, day out, are unprecedented. Even in normal circumstances, frontline work can take its toll not just on your physical health, but also on your mental wellbeing.
“From my time with the air ambulance, I know all too well how determined frontline workers are to put a brave face on and keep going.”
William has worked as an air ambulance pilot and has spoken out about how the pressures of the job sometimes took a toll on his mental health – causing him “enormous sadness”.
He added in the Our Frontline video: “When you spend all day taking care of others it is easy to forget that you need to take care of yourself too.
“But it’s OK to say when you’re not feeling OK. There is support available to you, if and when you need it.”
Our Frontline was launched a few weeks ago by mental health charities Mind, Samaritans and Shout, as well as Hospice UK and the Royal Foundation.