The Wiltshire city has been at the centre of a probe of international importance since Mr Skripal, 66, and his daughter, Yulia, 33, were discovered unconscious on a bench.
The Mill pub and Zizzi restaurant where the pair dined before falling unconscious, as well as a number of nearby businesses, have been sealed off since the incident.
While residents do not fault the police, they want more be done to help those businesses that are still open but have been left out of pocket.
Darren James, chairman of the Salisbury and District Trade Union Congress, told the Standard: "We need clear guidance on who is going to foot the bill. Keep it simple. These people need help and they need it urgently.
"I understand the Mill pub, which is owned by Greene King, is paying staff. But of course, they're able to because they are part of a huge, nationwide business.
"And this all came in the week of that horrendous snow we had which caused a lot of closures. It's just been one thing after the other for businesses around here."
Wiltshire Council has approved a £20,000 donation to a hardship fund to support local entrepreneurs.
Deputy leader John Thompson said: "We've visited 50 businesses to help them to apply for business rate relief and our officers are on the ground doing that. It's not a matter us waiting for them to come to us we're going to businesses.
"We're also working with HMRC to take a helpful and supportive approach to any VAT or tax issues that businesses may have."
Despite these efforts, many fear it may be too little too late.
Marie Roberts, who runs the area's Harnham physiotherapy clinic, said: "Ever since the attempted murder and subsequent closures and cordons in Salisbury, local independent shopkeepers are struggling to stay afloat.
"This follows a quiet period caused by heavy snow...I met a shop assistant earlier a few days ago who told me their store had been deserted the past week.
"People seem to still think Salisbury is a ghost town and small businesses are really suffering."
While Daniel Styles, who runs a popular flower stall, told local Spire FM he made a huge loss on what would ordinarily be one of his biggest days of the year - Mother's Day.
He said: "I guess people are scared to come in...Mother's Day weekend is normally one of the biggest weekends of the year for us.
"We normally make around £12,000 and we only made two or three grand...We're trying to be patient. We know it's a big incident."
Local newspaper the Salisbury Journal launched a campaign in the wake of the attack, #SalisburyisOpen, hoping to support businesses which have suffered as a result of the police investigation.
Bill Browne, the Journal's publisher, said: "We have not lost focus. This is having a very real impact on those who depend on trade in this town for their livelihoods.
"We are inviting readers, businesspeople and anyone we can reach to share the Salisbury is Open message with as many people as possible."
In a visit to the city on Thursday, Prime Minister Theresa May met with local businesses and urged people to "come and enjoy Salisbury".
She said: "There has been, as I understand it, a fall in the number of people visiting Salisbury, but the important message I’ve had today is that Salisbury is open.
"It’s a great city to visit and we want to see people coming here and continuing to enjoy the beauty and the history of this wonderful city.
"Salisbury has tremendous resilience, great spirit and they look forward to welcoming people into this city."
The Prime Minister revealed she would expel 23 Russian diplomats earlier this month in response to Russia's failure to explain the attack on Mr Skripal.
Wiltshire police say they cannot be sure how long it will be before cordons around parts of the Maltings shopping centre will be lifted.
Chief Constable Kier Pritchard said: "It's of vital importance that we maintain the integrity of those crime scenes in the interests of public safety."
Mr Skripal and his daughter remain in hospital in a serious condition.