The attack on a compound in southern Pakistan housing the ISI office was carried out shortly after 'iftar', the meal that ends the daily fast in the holy month of Ramzan.
Geo News channel quoted intelligence sources as saying that at least four terrorists, wearing suicide vests and carrying automatic weapons, were involved in the attack.
One attacker rammed an explosives-laden vehicle into the wall of the Inter-Services Intelligence office at Barrage Colony in Sukkur, Sindh's third largest city located 500 km from the financial hub of Karachi.
The others stormed into the regional headquarters of the ISI, lobbed grenades and exchanged fire with personnel inside. Two attackers blew themselves up inside the building while another was captured, Geo News reported.
At least five persons were killed and 38 others, including women and children, injured in the attack, officials said.
Witnesses said they had heard at least four blasts within the high-security compound that houses the ISI office and residences of intelligence, police and civil officials.
Footage on television showed the ISI office and other buildings were extensively damaged. The walls and ceilings of the buildings collapsed and several cars were destroyed.
A police official in Sukkur, who did not want to be named, told PTI that buildings housing government offices were razed by the blasts.
Deputy Inspector General of Police Javed Odho told the media the ISI office was the target of the attack. "The blasts took place in a compound that houses the offices of senior police officials and an intelligence agency," he said.
Security forces and paramilitary Pakistan Rangers surrounded the area and conducted a search operation.
Sindh Information Minister Sharjeel Memon described the attack as unfortunate and said the Barrage Colony also housed residences of government officials, including judges.
No group claimed responsibility for the attacks. The Taliban have targeted offices of the ISI and other security agencies in Punjab and Khyber-Pakhtunkhwa provinces but such attacks are rare in Sindh.
Two separate blasts kill seven in Pakistan
Pakistan troops violate ceasefire in Jammu
Bomb targeting senior judge kills 7 in Pakistan
Naxal cocktail: Stolen guns, extorted money, violent threats
Bomb targeting senior judge kills 7 in Pakistan