Eastern boundary upwelling systems (
EBUS
s) are among the most productive marine environments in the world. The Canary Current upwelling system off the coast of Mauritania and Morocco is the second most productive of the four
EBUS
, where nutrient‐rich waters fuel perennial phytoplankton blooms, evident by high chlorophyll a concentrations off Cape Blanc, Mauritania. High primary production leads to eutrophic waters in the surface layers, whereas sinking phytoplankton debris and horizontally dispersed particles form nepheloid layers (
NL
s) and hypoxic waters at depth. We used Catalyzed Reporter Deposition Fluorescence In Situ Hybridization (
CARD
‐
FISH
) in combination with fatty acid (measured as methyl ester;
FAME
) profiles to investigate the bacterial and archaeal community composition along transects from neritic to pelagic waters within the “giant Cape Blanc filament” in two consecutive years (2010 and 2011), and to evaluate the usage of
FAME
data for microbial community studies. We also report the first fatty acid profile of
Pelagibacterales strain
HTCC
7211 which was used as a reference profile for the
SAR
11 clade. Unexpectedly, the reference profile contained low concentrations of long chain fatty acids 18:1
cis
11, 18:1
cis
11 11methyl, and 19:0 cyclo11–12 fatty acids, the main compounds in other
Alphaproteobacteria
. Members of the free‐living
SAR
11 clade were found at increased relative abundance in the hypoxic waters in both years. In contrast, the depth profiles of
Gammaproteobacteria
(including
Alteromonas and Pseudoalteromonas
),
Bacteroidetes
,
Roseobacter
, and
Synechococcus
showed high abundances of these groups in layers where particle abundance was high, suggesting that particle attachment or association is an important mechanisms of dispersal for these groups. Collectively, our results highlight the influence of
NL
s, horizontal particle transport, and low oxygen on the structure and dispersal of microbial communities in upwelling systems.