The blast ripped through the Shia mosque in Lakhi Dar area of Shikarpur district when about 400 worshippers lined up to offer weekly Friday prayers.
Provincial health minister Jam Mehtab said that 61 people were killed and over 50 injured in the attack.
SSP Saqib Memon said that a severed head and other body parts of an unidentified bomber were sent for DNA testing.
Police said that upto 7 kgs of deadly RDX explosive was used in the bombing.
Shia representative body Majlis Wahdatul Muslimeen (MWM) is observing a strike across Sindh while the provincial government is observing a day of mourning.
Sindh Chief Minister Qaim Ali Shah visited the site of the explosion and announced Rs 2 million compensation for the victims' families.
Meanwhile, hundreds of Shias and members of civil society were gathering in different areas of provincial capital Karachi to protest.
So far only a few bodies have been buried and preparations are being made to bury rest of the victims today.
It was the second major attack on the minority Shia community after eight people were killed in a suicide attack at a mosque in Rawalpindi on January 10.
The attack came as Pakistan increased pressure on militant groups after last month's grisly Peshawar school attack that killed 150 people, mostly schoolchildren.
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