Three others were wounded in the explosion, which occurred on Thursday "during a mission" in Nord Bignona, near the border with Gambia, the army's public relations unit said on X, formerly Twitter.
Senegalese President Macky Sall, also on X, paid "homage to the memory" of the four soldiers who "fell on the field of honour".
The pro-independence rebels "are laying mines in the roads to protect their criminal economy," a military source told AFP.
"In recent months, we have detected and neutralised several devices of this type without incident. Unfortunately, this time there have been casualties", the source added.
The army has for several months been carrying out security operations against separatist rebels of the Movement of Democratic Forces of Casamance (MFDC), who want independence for the region that also borders Guinea-Bissau.
One of Africa's oldest active rebellions, the MFDC has led a low-intensity separatist campaign since 1982 that has claimed several thousand lives.
The conflict was mostly dormant until Senegal launched a major offensive in 2021 to drive out the rebels.
The Senegalese army last released information about the death of one of its soldiers in January this year. However, military operations have continued since.
Casamance, Senegal's southernmost region, is almost separated from the rest of the country by the tiny state of Gambia.
It has a distinct culture and language derived from its past as a former Portuguese colony.
President Sall, who was re-elected for a second term in 2019, has said that ending the rebellion is a priority.
In recent years, the government has begun returning Casamance residents displaced by the conflict after announcing the destruction of several rebel bases.
The government and rebels have signed several peace agreements, which quickly became obsolete.
One was signed in August 2022 in Guinea-Bissau between rebel leader Cesar Atoute Badiate, head of a MFDC unit, and an emissary of Sall, following mediation by Guinea-Bissau's head of state, Umaro Sissoco Embalo.
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