Reaction time (RT) is chiefly longer when people lie. However, the baseline speed in answering questions and the amount of RT prolongation during lying show considerable amount of inter-individual variability. In the current study, we exploited this fact to glean insights on the contribution of each lie-related brain region to hampering of response speeds when people try to be deceitful. In an event-related fMRI session, participants were interrogated by yes-no autobiographical questions and were instructed to intentionally provide false responses to a pre-selected subset of questions. Data from twenty healthy volunteers were analyzed. Baseline speed [RTtruth] and relative appended lie RT [(RTlie − RTtruth) ∕ RTtruth] measures were calculated for each participant and were included in the group level analysis of [lie > truth] BOLD contrasts. Lying RTs were significantly longer than truth telling RTs. Lie-related increase in activity of right ventrolateral prefrontal cortex (VLPFC) and bilateral paracingulate cortex correlated with the baseline speed of participants, while the increase in activity of Left VLPFC, left lateral occipital cortex and bilateral anterior cingulate areas directly correlated with the amount of lying reaction time cost. Activity within bilateral posterior cingulate cortex and right insular cortex inversely correlated with lying RT-cost. Bilateral supplementary motor areas, internal capsule white matter and left angular gyrus showed lie-related increase in activity but did not correlate with either of behavioral measures. Provisional implications regarding the contribution of these regions to RT prolongation and their cognitive role in deceitful behavior are discussed.