Realty, IT and bank stocks led eight of the 12 BSE sectoral indices lower.
Infosys and ICICI Bank were the biggest drag on the index. Bajaj Auto and Mahindra & Mahindra were among the major Sensex losers.
BHEL and Coal India led the 14 index gainers and Sesa Sterlite firmed up after it was allowed to resume mining operations in Karnataka after two years.
The S&P BSE Sensex opened higher and rose to 21,304.70 on initial support on the back of foreign capital inflows and firm Asian cues.
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However, it declined to 21,089.21 before ending at 21,143.01, a loss of 50.57 points or 0.24 per cent. It had gained 160.87 points in the previous two sessions.
The CNX Nifty on the National Stock Exchange fell 22.70 points, or 0.36 per cent, to 6,291.10. The SX40 on the MCX Stock Exchange slid 41.89 points to 12,552.70.
Rate-sensitive stocks were down after Rajan said high inflation is limiting the central bank's ability to boost growth with an accommodative monetary policy.
Foreign institutional investors bought shares worth a net Rs 295.76 crore last Friday, according to provisional data from the stock exchanges.