Severn Hospice estimates its losses so far this year to be at least £500,000, and said the figure is expected to rise in coming months.
When the pandemic first hit and the hospice was forced to close all of its 28 shops, including its flagship megastore in Shrewsbury, as well as cancel all fundraising events, more than £100,000 a week was being lost.
The hospice also said the national rise in positive coronavirus cases was being seen within its staff.
Heather Tudor, chief executive, said the total loss of funds to the hospice would not be known for months.
She said: "The current picture is that with increased case numbers nationally, we're seeing increased cases within our staffing, and that is affecting things slightly.
"The lockdown for us as a charity is continuing to impact on our finances greatly.
"As we move through the year with continued periodic lockdowns we're getting more concerned about what the overall deficit will look like, and we're not going to know that until at least another month or two.
"We have income targets for our shops that have been completely decimated by the need to lockdown and control and limit our activities.
"We hoped as we reopened our shops a couple of months ago we would be heading towards those targets but the latest lockdown has completely squashed these hopes."
Mrs Tudor added the roll-out of the vaccine "gives hope" that services may return to some normality soon, although bosses were already looking at ways to save money going forward.
"I think it's being rolled out at a pace that gives me hope we'll move to more of a normality, although it's not going to be a quick process.
"Severn Hospice has worked very hard over the years to build its reserves so we have them to fall back on in the short term, but as we move into the next financial year, we may find ourselves in the position where we need to reduce costs – the big worry is how that'll impact our ability to deliver our services.
"We don't want it to get to that but we have to start thinking about it now in case we have to make those decisions."
The hospice has to raise £2 for every £3 it spends on care and despite the financial hardship, workers have been able to continue to deliver care.
"In terms of delivering our services, nothing has changed," said Mrs Tudor.
"We can't stop caring and we've worked really hard to maintain our essential services throughout.
"I'm incredibly proud of our staff. If we can't deliver the services our poor patients can't get the care they need and will end up in hospital – that's the last thing they want, the last thing we want and the last thing the NHS needs."