Mohit has aggravated a shin problem and will play no further part in the five-match rubber, which began on Wednesday.
West Indies won the opening match by 124 runs and Ishant, who last played an ODI in January, will be tasked with helping India fight back in Saturday's second contest at Delhi's Feroz Shah Kotla.
Ishant was a member of the India Test squad that toured England earlier this year and returned career-best figures of 7-74 as MS Dhoni's side claimed a notable victory at Lord's in July.
However, the rangy seamer has been out of favour in 50-over cricket since the beginning of 2014, when he proved expensive in successive defeats at the hands of New Zealand.
Ishant has played 72 ODIs in all, claiming 102 wickets at an average of 31.