The purpose of this study is to investigate determinants of banks profitability in CBE by using time series data of CBE from year2003 to 2015. The research has econometric research design. The study used quantitative research approach and secondary financial data are analyzed by using Vetcor Auto Regressive Model (VAR), for the bank profitability was measured by Return on Asset (ROA). OLS method was applied to investigate the impact of bank size, managerial efficiency, liquidity, credit risk, real GDP growth rate, and annual inflation rate. The empirical results shows that bank specific factors; bank size, managerial efficiency, credit risk and macro-economic factors; level of GDP and annual inflation rate have a strong influence on the profitability of banks. The empirical study shows that, all explanatory variables in this study have negative effect on the profitability measure except GDP and inflation rate. In addition to this, without liquidity all explanatory variables are statistically significant. Management bodies of CBE should strive to strengthen the bank specific factors like capital position, managerial efficiency, credit risk, asset quality, and bank size.