Hope House, which has a hospice in Oswestry as well as in Conwy, has already lost more than £1.25 million of income since April.
It said that news it must now close its six charity shops in Wales from Friday until November 9 will add to the losses.
Chief Executive Andy Goldsmith said the hospices have remained open during the pandemic, delivering vital care and support to terminally ill local children and their families.
He said: “We have made it a priority to provide end of life care, care after death and crisis care, while developing new virtual hospice services via online platforms, phone and post to ensure support is there for children, siblings and families who are sheltering at home.
“Our services usually cost in the region of £500,000 a month to provide and most of that cost is usually met via donations, fundraising, our lottery and our shop sales.
“But, with more shop closures and all but virtual fundraising events cancelled for the rest of this year we are experiencing an unprecedented fall in income at a time when we are facing additional costs such as the need for full PPE to nurse the children safely.”
Mr Goldsmith went on to say that September had been the first month that all 14 of the charity’s shops across the region had opened, having been reorganised and fitted out to be Covid compliant and safe for customers, volunteers and staff.
They had even returned a small profit for the first time since before the initial lockdown.
“Unfortunately Llandudno and Welshpool, which are two of our most profitable shops, are affected by the latest lockdown in Wales at a time when they are usually becoming busy with Christmas card sales,” he added.
“We are about to write to all our supporters appealing to them to help us at least recoup some losses by the end of the year by sending donations and buying our annual Christmas raffle tickets.
“We realise that many people are suffering financially in these challenging times, but for those people who are able to help us we promise that your support will enable us to help children and families at a time when that support has never been more needed.”
For details of how to donate, buy Christmas cards or join the charity's lottery call the fundraising office on 01691 671671.