On the second anniversary of the first national lockdown, Mr Johnson said those who died over the past two years “will never be out of our hearts and minds”, as the nation prepared to gather in reflection.
The country will pause on Wednesday in remembrance of those who have died during the crisis, as part of a series of events organised by the end-of-life charity, Marie Curie.
A minute’s silence will be held at midday, and people are being encouraged to shine a light or display flowers in their window at 8pm.
There will also be an online map with virtual walls of reflection where people can pay tribute to their loved ones.
More than 350 organisations are supporting the day of reflection, during which landmarks across the UK will be lit up in yellow.
“The toll this pandemic has taken across the globe is immeasurable," Mr Johnson said.
"The National Day of Reflection is a chance to come together, mourn and offer our collective support and sympathies to all those grieving.
“It’s also a chance to thank everyone who cared for us throughout.
“I saw first-hand the heroic efforts of NHS staff and I pay tribute to them — the grief counsellors, charity workers and friends and families — as we pause to remember those we have lost.”
Labour leader Sir Keir Starmer said the spirit and generosity shown by charities, community and faith groups “are exemplary examples of British values”.
Mr Starmer said his thoughts were with those who lost loved ones.
“As we emerge from the pandemic, we must not forget the long tail of grief it leaves and the profound impact it has had on us all," he said.
“For so many, life is now permanently altered and we won’t forget it.”
Mr Johnson and Mr Starmer will be marking the anniversary privately.
First Minister of Scotland Nicola Sturgeon, First Minister of Wales Mark Drakeford and Minister for Health for Northern Ireland Robin Swann are also supporting the day.
The Covid19familiesuk group will be tying yellow ribbons to Westminster Bridge in London from 10am, and London Ambulance Service is holding a service in its memorial garden.
Data published on Tuesday by the Office for National Statistics showed a total of 188,078 deaths have occurred in the UK with Covid-19 mentioned on the death certificate.
Ruth May, NHS England’s chief nursing officer, said she was “eternally thankful and proud” of everything health and care staff have achieved.
“I have seen NHS staff across the length and breadth of the country step up to the task that has faced them, delivering the best possible care to their patients and supporting each other during some very difficult times," Ms May said.
“That is why it is so important that we get together and reflect as a nation on the impact Covid-19 has had on us all, especially those who are no longer with us.”
Marie Curie chief nurse Julie Pearce said: “While life is beginning to return to normal for some people, several million people are still living with the trauma of loss, and not being able to grieve properly.
“Let’s take time to connect and show support for the millions of people who are grieving, and remember the family, friends, neighbours and colleagues we’ve lost over the last two years.”