The deaths came amid anti-government protests against planned constitutional reforms that would allow President Faure Gnassingbe to remain in office until 2030. His family has ruled the West African nation since 1968.
Three people were shot dead in the country's second city, Sokode, and another was killed in the capital Lome, the government said on Wednesday. The violence later spread to several other cities in the north.
The protests were triggered in part by the arrest of an imam on Monday in Sokode on charges of inciting his followers to violence.
Opposition parties refused to cancel demonstrations on Wednesday and said they would go ahead with protests also on Thursday, disregarding a government ban on weekday protests on security grounds.
Wednesday was the first of two days of protests by the opposition demanding the reinstatement of Togo's original constitution, which they say would bar President Faure Gnassingbe from a fourth term in 2020.
Since the first protests on August 18, 12 people have been killed, most of them teenagers.
The opposition coalition - the National Alliance for Change (ANC) - claimed on Wednesday there had been "two deaths, including an 11-year-old schoolboy" as well as "at least 20 serious injuries" in Lome. Around 60 people were reportedly detained. Amnesty International said that at least 28 people of over 100 arrested have been convicted in connection with the protests.
Streets in central Lome were blocked and most shops shut in the commercial area of Deckon, the French news agency AFP reported.
"Security forces aren't the only ones in possession of weapons, so it's difficult to say who fired," security minister Colonel Yark Damehame told reporters.
In Be - an opposition stronghold southeast of the capital - security services reportedly fired teargas and rubber bullets at crowds seeking to join up with the planned march to the National Assembly.
Groups of youths blocked main roads around the district with makeshift barricades of stones, burning tyres, tree trunks or burned-out cars.
Amnesty International's country director, Aime Adi said the army had locked down the area and that there were small groups of 'militiamen' with sticks warning people not to go to the march.
Eric Dupuy, spokesman for the main opposition ANC said assembly points for the march had been "taken over by the security forces." But he added: "We are going to march whatever the cost and intimidation."
Gnassingbe won't budge
The controversial constitutional reform to limit presidential terms to two will be decided by popular referendum after the bill failed to win approval from parliament following a boycott by opposition lawmakers last month.
The referendum is to be held in the coming months but the opposition has complained that the new measures are not retroactive.
The president won elections in 2005, 2010 and 2015. He would still be able to contest the elections in 2020 and 2025. Gnassingbe would thus be eligible for two further five-year terms under the terms of the proposed bill, leaving him in power until 2030.
Gnassingbe's family has ruled the West African nation since 1968.