When an exothermic reaction occurs, the energy in the chemical bonds of the reactants is partially transferred to the chemical bonds of the products. The remaining energy is released as heat.
For example:
$$\mathrm{N_2 + 3H_2 \to 2NH_3} \qquad \Delta G^\circ = -32.96 \,\rm kJ/mol$$
Therefore, when $1\,\rm mol$ of nitrogen reacts with $3\,\rm mol$ of hydrogen (under standard conditions), we get $32.96\,\rm kJ$ of heat.
Now, applying $E=mc^2$, this works out to be
$$m = 32.96 \times (3 \times 10^{-8})^2 = 2.96 \times 10^{-14} \,\rm kg \quad \text{or} \quad 29.6\, pg$$
Does this relationship hold? Do the products of an exothermic reaction really weigh ever so slightly less than the reactants?
In a more general sense, does removing energy from a system decrease its mass (or vice versa)?